Biomedicines最新文献

{"title":"Glucocorticoid Insensitivity: Is It a Question of Time and Place?","authors":"Christopher Lambers, Michael Roth","doi":"10.3390/biomedicines13061418","DOIUrl":"10.3390/biomedicines13061418","url":null,"abstract":"<p><p><b>Background:</b> Glucocorticoid insensitivity is a problem for the therapy of chronic inflammatory lung diseases, such as asthma and chronic obstructive pulmonary disease (COPD). Both are non-communicable chronic inflammatory lung diseases with worldwide increasing incidences. Only symptoms can be controlled by inhaled or systemic glucocorticoids, often combined with β2 agonists and/or muscarinic receptor antagonists. The therapeutic effect of glucocorticoids varies between individuals, and a significant number of patients do not respond well. It is believed that only protein-free circulating unbound glucocorticoids can enter cells by diffusion and achieve their therapeutic effect by binding to the intracellular glucocorticoid receptor (GR), encoded by the NR3C1 gene, for which over 3000 single-nucleotide polymorphisms have been described. In addition, various GR protein isoforms result from 11 transcription start sites, and differential mRNA splicing leads to further GR protein variants; each can be modified post-translational and alter steroid response. To add more variety, some GR isoforms are expressed cell-type specific or in a sub-cellular location. The GR only functions when it forms a complex with other intracellular proteins that regulate ligand binding, cytosol-to-nuclear transport, and nuclear and cytosolic action. Importantly, the timing of the GR activity can be cell type, time, and condition specific. These factors are rarely considered when assessing disease-specific loss or reduced GR response. <b>Conclusions</b>: Future studies should analyze the timing of the availability, activity, and interaction of all components of the glucocorticoid signaling cascade(s) and compare these factors between non-diseased and diseased probands, applying the combination of all omics methods (250).</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 6","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12191323/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144494191","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Point-of-Care Ultrasound Use in Hemodynamic Assessment.","authors":"Ahmed Noor, Margaret Liu, Alan Jarman, Travis Yamanaka, Malvika Kaul","doi":"10.3390/biomedicines13061426","DOIUrl":"10.3390/biomedicines13061426","url":null,"abstract":"<p><p>Hemodynamic assessment is critical in emergency and critical care for preventing, diagnosing, and managing shock states that significantly affect patient outcomes. Point-of-care ultrasound (POCUS) has become an invaluable, non-invasive, real-time, and reproducible tool for bedside decision-making. Advancements such as Doppler imaging, advanced critical care ultrasonography, and transesophageal echocardiography (TEE) have expanded its utility, enabling rapid and repeatable evaluations, especially in complex mixed shock presentations. This review explores the role of POCUS in hemodynamic monitoring, emphasizing its ability to assess cardiac output, filling pressures, and vascular congestion, facilitating shock classification and guiding fluid management. We highlight an extensive array of POCUS techniques for evaluating right and left cardiac function and review existing literature on their advantages, limitations, and appropriate clinical applications. Beyond assessing volume status, this review discusses the role of POCUS in predicting fluid responsiveness and supporting more individualized, precise management strategies. Ultimately, while POCUS is a powerful tool for rapid, comprehensive hemodynamic assessment in acute settings, its limitations must be acknowledged and thoughtfully integrated into clinical decision-making.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 6","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12189778/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144494272","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unraveling the Roles of Macrophages in Vascularized Composite Allotransplantation.","authors":"Hui-Yun Cheng, Madonna Rica Anggelia, Cheng-Hung Lin","doi":"10.3390/biomedicines13061425","DOIUrl":"10.3390/biomedicines13061425","url":null,"abstract":"<p><p>The phenotypic heterogeneity and functional diversity of macrophages have been increasingly appreciated, particularly regarding their roles as innate immune cells in shaping transplantation outcomes. However, their functions in vascularized composite allotransplantation (VCA) remain underexplored. In this review, we first describe the development of macrophages and the heterogeneity of macrophage differentiation, then present current insights into macrophages' involvement across key stages of VCA, including ischemia-reperfusion injury at the peri-transplantation stage, and the outcomes following transplantation, including acute rejection, chronic rejection, and development of transplantation tolerance. The existing evidence supports that macrophages significantly influence both short- and long-term VCA graft survival. The presence of vascularized bone marrow within some VCA grafts further suggests the involvement of donor bone marrow-derived macrophage population and adds another layer of complexity to immune dynamics. Collectively, current understanding highlights the macrophage as a promising target for therapeutic intervention and warrants continued investigation into their diverse functions and potential for improving VCA outcomes.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 6","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12189788/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144494380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Comparative Analysis of Radiological Imaging and Surgical Treatments for Maxillary Artery Pseudoaneurysms, Based on a Literature Review and Our Clinical Experience.","authors":"Kinga Samól, Adam Michcik, Barbara Wojciechowska, Adam Polcyn, Łukasz Garbacewicz, Barbara Drogoszewska","doi":"10.3390/biomedicines13061410","DOIUrl":"10.3390/biomedicines13061410","url":null,"abstract":"<p><p><b>Background/Objectives</b>: A pseudoaneurysm forms as a result of disruption of all artery wall layers. In the head and neck, they are most commonly found in the maxillary artery. Due to their location and associated symptoms, detailed radiological imaging is necessary to determine the nature and extent of lesions. Various treatment methods are available. <b>Methods</b>: To systematize symptoms, diagnostics, and treatment methods, a literature review from databases spanning 2014 to 2024 was conducted, with 30 articles included in the study. <b>Results</b>: The factors that caused MAPs included facial trauma (n = 33; 66%), iatrogenic surgical procedures (n = 14; 28%), head and neck radiotherapy (n = 1; 2%), infection (n = 1; 2%), and one case due to an idiopathic factor (n = 1; 2%). Diagnostic imaging included computed tomography with contrast, magnetic resonance imaging, and angiography. Treatment methods used: endovascular embolization (n = 44; 88%), surgical resection (n = 3; 6%), cauterization (n = 2; 4%), and compression tamponade (n = 1; 2%). Interestingly, three of the cases were treated with endoscopic access (6%). <b>Conclusions</b>: It can be concluded that the most common cause of MAPs is trauma to the facial skeleton, and the most frequently used treatment method is endovascular embolization. Given the need for detailed MAP imaging and treatment in specialized invasive radiology departments, patients with MAPs should be treated in multidisciplinary clinical centers.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 6","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12190534/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144494104","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Peptide-Based Nanoparticle for Tumor Therapy.","authors":"Phonpilas Thongpon, Menghuan Tang, Zhaoqing Cong","doi":"10.3390/biomedicines13061415","DOIUrl":"10.3390/biomedicines13061415","url":null,"abstract":"<p><p>Cancer treatment continues to face significant challenges due to the limitations of conventional therapies, including non-specific toxicity, poor bioavailability, and drug resistance. Nanotechnology, particularly peptide-based nanoparticles (NPs), is increasingly recognized as a valuable strategy to address these obstacles. Peptides provide a versatile platform offering high biocompatibility, specificity, biodegradability, and minimal immunogenicity, making them ideal for targeted cancer therapies. This review comprehensively examines recent advancements in peptide-based nanoparticle systems, highlighting the mechanisms driving peptide self-assembly, such as amphiphilicity, non-covalent interactions, and metal coordination. It distinguishes between non-bioactive peptide nanoparticles, which primarily serve as drug carriers, and bioactive peptide nanoparticles, which integrate targeting peptides, cell-penetrating peptides (CPPs), and therapeutic peptides to enhance specificity, internalization, and anticancer efficacy. Emphasis is placed on innovative designs that exploit active targeting, stimuli-responsive release, and immunomodulatory strategies to maximize therapeutic outcomes while minimizing side effects. Despite promising preclinical outcomes, the clinical translation of peptide nanoparticles struggles with challenges involving stability, delivery efficiency, scalability, regulatory compliance, and manufacturing complexity. The review concludes by outlining future directions, emphasizing personalized nanomedicine, combination therapies, and advanced peptide engineering as crucial pathways toward successful clinical implementation.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 6","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12190518/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144494264","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimizing Nephron Performance: The Old, the New, and the New-Old Diuretic Therapies.","authors":"Flavio D Fuchs, Guilherme S Procianoy, Leonardo G Bottino, Sandra C Fuchs, Paul K Whelton","doi":"10.3390/biomedicines13061413","DOIUrl":"10.3390/biomedicines13061413","url":null,"abstract":"<p><p>Pharmacological influence on nephron function has modified the clinical course of hypertension, heart failure, and chronic kidney disease. (CKD). This is a review of the efficacy of old diuretics and the incremental efficacy of new diuretics in managing hypertension, heart failure, and CKD, concluding with new evidence on the effectiveness of old agents. The efficacy of \"older\" diuretic agents, such as thiazide and loop diuretics, on heart failure and CKD has been primarily explored in nonrandomized studies. However, the efficacy of these agents and indapamide, a slightly newer but still \"old\" diuretic in preventing blood pressure-related cardiovascular disease, has been demonstrated in randomized controlled trials. Potassium-sparing agents counteract some of the adverse effects of thiazides and have been shown to prevent cardiovascular events in patients with heart failure. Newer drugs with a diuretic effect, such as gliflozins, act through a new mechanism of action in the kidney and have shown efficacy in controlling symptoms and preventing cardiovascular events in patients with heart failure, regardless of diabetes. Furthermore, gliflozins have prevented the progression of chronic kidney disease in patients with and without diabetes mellitus. New evidence detailing the efficacy of old agents has emerged. Chlorthalidone had a large blood-pressure-lowering effect in patients with stage IV CKD. Acetazolamide was effective in accelerating the clinical control of patients with acute heart failure, including patients with some reduction in kidney function. We anticipate investigating the comparative impact of combining different agents to optimize nephron function in the future.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 6","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12189965/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144494258","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacokinetics and Ex Vivo Activity of 7-Methylxanthine, an Inhibitor of Monosodium Urate Crystallization.","authors":"Miguel D Ferrer, Jaume Dietrich, Bernat Isern, Maria Del Mar Pérez-Ferrer, Joan Albertí, Félix Grases, Antònia Costa-Bauzà","doi":"10.3390/biomedicines13061411","DOIUrl":"10.3390/biomedicines13061411","url":null,"abstract":"<p><p><b>Background/Objectives:</b> 7-Methylxanthine (7-MX) is a naturally occurring metabolite of caffeine and theobromine that can inhibit the crystallization of monosodium urate (MSU) and may be useful for the prevention or treatment of gout. However, the pharmacokinetics and ex vivo activity of 7-MX remain poorly characterized. <b>Methods</b>: The present study assessed the pharmacokinetics of 7-MX in Sprague Dawley rats following a single oral dose (30 mg/kg), and the ex vivo inhibition of MSU crystallization by 7-MX in rat plasma after the repeated administration of oral 7-MX. <b>Results</b>: The pharmacokinetic analysis showed that 7-MX reached peak plasma concentration (C_max ≈ 30 µM) at 30 min after administration (t_max), the terminal half-life was approximately 1.4 h, and there was no evidence of accumulation after repeated daily dosing. After repeated administration, the relationship between dose (30 or 60 mg/kg) and plasma concentration was proportional. In vitro and ex vivo crystallization assays demonstrated that 7-MX inhibited MSU crystallization in a concentration-dependent manner. The in vitro studies showed that 100 µM 7-MX inhibited up to 74% of MSU crystallization under supersaturated conditions (400 mg/L urate). The ex vivo experiments indicated that plasma from rats that received 30 or 60 mg/kg of 7-MX had 41.4% and 52.6% inhibition of crystallization, consistent with the measured plasma concentrations. <b>Conclusions</b>: These findings confirm that oral administration of 7-MX to rats led to a plasma level that was sufficient to decrease MSU crystallization in plasma, and there were no observable toxicities. These results support the potential of 7-MX as a safe oral treatment for gout, especially in combination with urate-lowering therapies, such as allopurinol. Further clinical investigations are warranted to confirm the therapeutic potential of 7-MX in humans.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 6","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12190732/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144494266","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Altered Expression of NK Receptors in Racially/Ethnically Diverse and Risk-of-Relapse Pediatric Acute Lymphoblastic Leukemia Patients.","authors":"Stephen Mathew, Roslin Jose George, Alexsis Garcia, Sheila Powers, Subhash Aryal, W Paul Bowman","doi":"10.3390/biomedicines13061412","DOIUrl":"10.3390/biomedicines13061412","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Acute Lymphoblastic Leukemia (ALL) is a cancer that predominantly affects white blood cells within the blood and bone marrow of adults and children. Currently, ALL is one of the most prevalent malignancies in pediatric patients and is most seen among Caucasian and Hispanic descent, with lower incidence in African American children. The goal of the study was to investigate the expression of immune cell receptors in racial/ethnic populations and risk factors for relapse that could potentially influence the pediatric ALL outcomes. <b>Methods:</b> Twenty healthy subjects and forty-two pediatric ALL subjects were enrolled in the study and whole-blood was collected at diagnosis and post-chemotherapy, and the cell surface expression of various immune receptors, including 2B4, CS1, LLT1, Nkp30, and NKp46, was determined by flow cytometry. <b>Results:</b> Very high-risk and high-risk of relapse ALL subjects showed increased expression of LLT1 on NK cells, T cells, and monocytes at diagnosis compared to healthy subjects. CS1 was also significantly overexpressed on monocytes of very-high risk ALL subjects both at diagnosis and after the end of chemotherapy as compared to healthy subjects. Also, there was a significantly increased expression of NKp30 on T cells of Caucasians as compared to Hispanics and African Americans at diagnosis, and downregulation of CS1 and LLT1 on T cells of Caucasians post-induction chemotherapy. <b>Conclusions:</b> The altered expression of immune receptors in racial/ethnic and risk stratified groups may provide insights into the immune surveillance mediated by T cells and NK cells against pediatric ALL.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 6","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12189698/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144494121","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prevalence, Evolution and Prognostic Factors of PASC in a Cohort of Patients Discharged from a COVID Unit.","authors":"Mariantonietta Pisaturo, Antonio Russo, Pierantonio Grimaldi, Caterina Monari, Simona Imbriani, Klodian Gjeloshi, Carmen Ricozzi, Roberta Astorri, Caterina Curatolo, Roberta Palladino, Francesco Caruso, Francesca Ambrisi, Lorenzo Onorato, Nicola Coppola","doi":"10.3390/biomedicines13061414","DOIUrl":"10.3390/biomedicines13061414","url":null,"abstract":"<p><p><b>Background and Aim</b>: PASC is a potentially debilitating clinical condition consisting of different general symptoms experienced by about 10% of patients with previous SARS-CoV-2 infection. Our study analyses a cohort of patients with a history of hospitalization for COVID-19 and aims to evaluate prognostic factors for experiencing PASC and to investigate the characteristics of patients experiencing PASC symptoms. <b>Methods</b>: This is an observational, monocentric retrospective study including all adult patients admitted to our COVID unit from 28 February 2020 to 30 April 2022, discharged alive, and having performed at least one follow-up visit at our post-COVID outpatient clinic after a minimum of three months from discharge. Patients who experienced persistent clinical manifestations or the development of new symptoms three months after the initial SARS-CoV-2 infection, with these symptoms lasting for at least two months with no other explanation, were defined as having PASC. <b>Results</b>: A total of 429 patients were discharged alive from our COVID Unit and 244 patients performed at least one follow-up visit in our outpatient clinic. Of these, 134 patients did not experience PASC, while 110 patients experienced PASC. Long-COVID patients were more frequently female (43.6% vs. 31.3%, <i>p</i> = 0.048), more frequently presented throat pain and headache at hospital admission (respectively 8.9% vs. 2.5%, <i>p</i> = 0.041 and 15.8% vs. 5%, <i>p</i> = 0.007), and were more likely to have a history of type 2 diabetes mellitus (25.5% vs. 13%, <i>p</i> =0.013). At the multivariable analysis, female gender, type 2 diabetes, and headache at admission were factors associated with PASC. All 46 patients who performed at least two different admissions in our outpatient clinic were divided in two groups: the first including the 16 patients who experienced a reduction or a resolution of symptoms related to COVID-19, the second comprising the 30 patients who experienced clinical worsening or persisting symptoms. Smoking habit was more represented among patients with stable or worsening symptoms (42.3% vs. 7.7%, <i>p</i> = 0.042); myalgias at admission were more frequent in the clinical worsening group (27.6% vs. 0%, <i>p</i>= 0.039); and a larger amount of patients who reported neuropsychiatric symptoms and respiratory symptoms were in the stable or worsening PASC symptoms group. <b>Discussion</b>: In conclusion, this study underscores the complexity of PASC, identifying female sex, Type 2 diabetes, and certain acute COVID-19 symptoms as potential predisposing factors for its development. PASC still represents a substantial public health challenge, and ongoing efforts are essential to better understand its underlying mechanisms and improve patient outcomes.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 6","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12191248/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144494202","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanisms Underlying Hyperexcitability: Combining Mossy Fiber Sprouting and Mossy Cell Loss in Neural Network Model of the Dentate Gyrus.","authors":"Dariusz Świetlik","doi":"10.3390/biomedicines13061416","DOIUrl":"10.3390/biomedicines13061416","url":null,"abstract":"<p><p><b>Background/Objectives</b>: A concussive head injury increases the likelihood of temporal lobe epilepsy through mechanisms that are not entirely understood. This study aimed to investigate how two key histopathological features shared by both TLE (temporal lobe epilepsy) and head injury-mossy fiber sprouting and hilar excitatory cell loss-contribute to the modulation of dentate gyrus excitability. <b>Methods</b>: A computational approach was used to explore the impact of specific levels of mossy fiber sprouting and mossy cell loss, while avoiding the confounding effects of concurrent changes. The dentate gyrus model consists of 500 granule cells, 15 mossy cells, 6 basket cells and 6 hilar perforant path-associated cells. <b>Results</b>: My simulations demonstrate a correlation between the degree of mossy fiber sprouting and the number of spikes in dentate gyrus granule cells (correlations coefficient R = 0.95, <i>p</i> < 0.0001) and other cells (correlations coefficient R = 0.99, <i>p</i> < 0.0001). The mean values (standard deviation, SD) and 95% CI for granule cell activity in the control group and percentage 10-50% of mossy fiber sprouting groups are 376.4 (16.7) (95% CI, 374.9-377.8) vs. 463.5 (24.3) (95% CI, 461.4-465.6) vs. 514.8 (32.5) (95% CI, 511.9-517.6) vs. 555.0 (40.4) (95% CI, 551.5-558.6) vs. 633.4 (51.8) (95% CI, 628.8-637.9) vs. 701.7 (66.2) (95% CI, 695.9-707.5). The increase in mossy fiber sprouting was significantly statistically associated with an increase in granule cell activity (<i>p</i> < 0.01). The removal of mossy cells led to a reduction in excitability within the model network (for granule cells, correlations coefficient R = -0.40, <i>p</i> < 0.0001). <b>Conclusions</b>: These results are generally consistent with experimental observations, which indicate a high degree of mossy fiber sprouting in animals with a higher frequency of seizures. Whereas unlike the strong hyperexcitability effects induced by mossy fiber sprouting, the removal of mossy cells led to reduced granule cell responses to perforant path activation.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 6","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12190842/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144494247","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}