Biomedicines最新文献

{"title":"Necrotizing Enterocolitis: A Comprehensive Review on Toll-like Receptor 4-Mediated Pathophysiology, Clinical, and Therapeutic Insights.","authors":"Asuka Ishiyama, Hee-Seong Jang, Jay M Dintaman, Johannes W Duess, Cody Tragesser, Chhinder P Sodhi","doi":"10.3390/biomedicines13092288","DOIUrl":"10.3390/biomedicines13092288","url":null,"abstract":"<p><p>This review integrates clinical, immunological, microbial, pathophysiological, and therapeutic perspectives on necrotizing enterocolitis (NEC)-a leading cause of morbidity and mortality in premature infants. We summarize the clinical burden and risk factors; elucidate key immune and cellular mechanisms, including TLR4 signaling, epithelial barrier dysfunction, and enteric nervous system involvement; and provide a concise overview of experimental models. We also highlight microbial dysbiosis, ischemia, multiorgan injury, and recent advances in pathogenesis, as well as current and emerging therapies such as probiotics, breast milk components, TLR4 inhibitors, and immunomodulators, emphasizing the need for a multidisciplinary approach to accelerate discovery and improve outcomes. Overall, this review bridges mechanistic insights to clinical applications and supports the pursuit of personalized NEC prevention.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 9","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12467431/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145173237","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":"The Association of Elevated Factor VIII and von Willebrand Factor (vWF) Levels with SYNTAX Score in Patients with Chronic Coronary Syndrome.","authors":"Predrag Djuric, Zorica Mladenovic, Zoran Jovic, Snjezana Vukotic, Marijan Spasic, Mirjana Mijuskovic, Brankica Terzic, Zoran Radojicic, Nina Radisavljevic, Marko Djuric, Dragan Djuric","doi":"10.3390/biomedicines13092284","DOIUrl":"10.3390/biomedicines13092284","url":null,"abstract":"<p><p><b>Background and Objectives:</b> Factor VIII (FVIII) and the von Willebrand factor (vWF) are key components of hemostatic balance. Disruption of the vWF-ADAMTS13 axis, characterized by elevated vWF and reduced ADAMTS13 activity has been implicated in thrombotic disorders, including COVID-19-asscoiated coagulopathy, where this imbalance correlates with disease severity and mortality. This study evaluated the relationship between plasma FVIII and vWF levels and the severity of coronary artery disease (CAD), as assessed by the SYNTAX score. <b>Methods:</b> We enrolled 82 patients with chronic coronary syndrome (CCS) and a positive treadmill test who underwent elective coronary angiography. Based on the SYNTAX score, patients were divided into three groups: Group I (≤22), Group II (23-32), and Group III (≥33). <b>Results:</b> FVIII levels varied significantly (Group I: 2.25 ± 0.75; Group III: 2.97 ± 0.95; <i>p</i> = 0.007), with an OR of 3.632 (95% CI: 1.116-11.826; <i>p</i> = 0.03). vWF levels differed significantly across SYNTAX groups (Group I: 1.16 ± 0.59; Group II: 1.52 ± 0.62; Group III: 1.49 ± 0.80; <i>p</i> = 0.040). vWF > 1.75 was more frequent in Groups II and III, with an odds ratio (OR) of 4.909 (95% CI: 1.429-16.864; <i>p</i> = 0.01) for Group III vs. Group I. Fibrinogen and C-reactive protein (CRP) were elevated in patients with SYNTAX scores ≥33. In multinomial logistic regression analysis, FVIII emerged as the sole independent predictor of CAD complexity (<i>p</i> = 0.004), while the vWF showed significance in pairwise comparison (Group II vs. Group I; OR = 3.433, <i>p</i> = 0.049). <b>Conclusions:</b> This study demonstrated significant differences in hemostatic and inflammatory biomarkers across SYNTAX score categories reflecting CAD severity in CCS patients. FVIII emerged as an independent predictor of CAD complexity, while the vWF demonstrated significant associations in specific subgroup comparisons. The observed vWF-ADAMTS13 axis dysregulation supports the rationale for investigating vWF-targeted therapeutics, including agents such as caplacizumab, in cardiovascular disease management. These findings require validation in larger studies.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 9","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12466950/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145172790","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":"Evolutionary Trajectory of <i>Plasmodium falciparum</i>: From Autonomous Phototroph to Dedicated Parasite.","authors":"Damian Pikor, Mikołaj Hurla, Alicja Drelichowska, Małgorzata Paul","doi":"10.3390/biomedicines13092287","DOIUrl":"10.3390/biomedicines13092287","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Malaria persists as a paradigmatic model of co-evolutionary complexity, emerging from the dynamic interplay among a human host, Anopheles vectors, and &lt;i&gt;Plasmodium falciparum&lt;/i&gt; parasites. In human populations, centuries of selective pressures have sculpted an intricate and heterogeneous immunogenetic landscape. Classical adaptations, such as hemoglobinopathies, are complemented by a diverse array of genetic polymorphisms that modulate innate and adaptive immune responses. These genetic traits, along with the acquisition of functional immunity following repeated exposures, mitigate disease severity but are continually challenged by the parasite's highly evolved mechanisms of antigenic variation and immunomodulation. Such host adaptations underscore an evolutionary arms race that perpetually shapes the clinical and epidemiological outcomes. Intermediaries in malaria transmission have evolved robust responses to both natural and anthropogenic pressures. Their vector competence is governed by complex polygenic traits that affect physiological barriers and immune responses during parasite development. Recent studies reveal that these mosquitoes exhibit rapid behavioral and biochemical adaptations, including shifts in host-seeking behavior and the evolution of insecticide resistance. Mechanisms such as enhanced metabolic detoxification and target site insensitivity have emerged in response to the widespread use of insecticides, thereby eroding the efficacy of conventional interventions like insecticide-treated bed nets and indoor residual spraying. These adaptations not only sustain transmission dynamics in intervention saturated landscapes but also challenge current vector control paradigms, necessitating the development of innovative, integrated management strategies. At the molecular level, &lt;i&gt;P. falciparum&lt;/i&gt; exemplifies evolutionary ingenuity through extensive genomic streamlining and metabolic reconfiguration. Its compact genome, a result of strategic gene loss and pruning, is optimized for an obligate parasitic lifestyle. The repurposing of the apicoplast for critical anabolic functions including fatty acid, isoprenoid, and haem biosynthesis highlights the parasite's ability to exploit host derived nutrients efficiently. Moreover, the rapid accumulation of mutations, coupled with an elaborate repertoire for antigenic switching and epigenetic regulation, not only facilitates immune escape but also accelerates the emergence of antimalarial drug resistance. Advanced high throughput sequencing and functional genomics have begun to elucidate the metabolic epigenetic nexus that governs virulence gene expression and antigenic diversity in &lt;i&gt;P. falciparum&lt;/i&gt;. By integrating insights from molecular biology, genomics, and evolutionary ecology, this study delineates the multifaceted co-adaptive dynamics that render malaria a recalcitrant global health threat. Our findings provide critical insights into the molecular arms race at the heart of ho","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 9","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12467193/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145172985","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":"Reimagining Oncologic Drugs in Atherosclerosis: Emerging Mechanisms and Therapeutic Potential.","authors":"George Liu, Guillaume De Vlaminck, Osayamen Atekha, Eric P Grewal, Rishab Ramapriyan, Gautam Agarwal","doi":"10.3390/biomedicines13092282","DOIUrl":"10.3390/biomedicines13092282","url":null,"abstract":"<p><p>Atherosclerosis is a chronic vascular disease that underlies the pathogenesis of both peripheral arterial disease and coronary artery disease, two of the leading causes of morbidity and mortality worldwide. Characterized by the accumulation of lipids, chronic inflammation, and fibrotic remodeling within vasculature, atherosclerosis involves a complex interplay of endothelial dysfunction, immune dysregulation, vascular smooth muscle cell proliferation, and maladaptive neovascularization. Increasing evidence now suggests that atherosclerosis has notable overlap with cancer biology, including sustained proliferative signaling, evasion of immune surveillance, angiogenesis, and resistance to cell death. These shared molecular features have prompted growing interest in the potential repurposing of oncologic treatments in the modulation of atherosclerotic disease. While preclinical data are promising, successful translation and integration of oncologic therapeutics will require overcoming critical barriers, including drug toxicity, long-term safety, regulatory constraints, and cost-effectiveness. Future work should focus on biomarker-guided patient selection, dose optimization, and targeted delivery systems to minimize off-target effects while enhancing efficacy.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 9","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12467425/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145173170","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":"The Prevalence of Diamine Oxidase Polymorphisms and Their Association with Histamine Intolerance Symptomatology in the Mexican Population.","authors":"Pamela Aguilar-Rodea, Viviana Mejía-Ramírez, Raúl Hernández-Munguía, Saúl Ramírez-Vargas, Diana Tovar-Vivar, Jaquelin Leyva-Hernández, Juan Carlos Nacar-Gutiérrez, Miriam Morales-Martínez, Aracely Palafox-Zaldivar","doi":"10.3390/biomedicines13092280","DOIUrl":"10.3390/biomedicines13092280","url":null,"abstract":"<p><p>Exogenous histamine obtained from the intake of histamine-rich food is mainly metabolized by the diamine oxidase enzyme (DAO). Histamine intolerance (HIT) is an alteration mainly caused by DAO deficiency, which is commonly associated with gastrointestinal, respiratory, cardiovascular, central nervous system, muscular, skeletal, and skin symptoms. Despite four single-nucleotide polymorphisms (SNPs) being mainly associated with DAO deficiency, the probability of inheriting these variants and their relationship with HIT in the Mexican population remain unknown. <b>Objective:</b> The aim of this study was to evaluate the prevalence of these SNPs and their relationships with HIT in the Mexican population, including both individual volunteers and family groups. <b>Methods:</b> Four SNPs related to DAO deficiency were detected in 112 volunteers; medical questionnaires were answered. <b>Results:</b> The prevalence of genetic DAO deficiency attributed to at least one risk allele was 78.57% (rs1049793 was the main SNP). Fifteen DAO SNP combinations were detected (the main rs2052129, rs10156191, rs1049742 (wild-type homozygotes), and rs1049793 (heterozygote), 31.25%). A total of 41.07% of the volunteers presented at least three symptoms in different systems related to HIT, of whom 84.78% presented at least one SNP. The DAO deficiency genetic risk score varied among individual volunteers and families. The highest probability of having a mutated homozygote was 11.8% (rs1049793). HIT symptoms varied among relatives sharing identical genotypes. <b>Conclusions:</b> The prevalence of SNPs related to DAO deficiency in the Mexican population correlates with globally reported data; however, further analysis with volunteers distributed throughout the country would be desirable. Although genetic predisposition was common, the presence of SNPs alone did not predict specific HIT symptoms. Multiple SNPs may increase the presence of HIT symptoms, regardless of the type of allele. These findings highlight the multifactorial nature of HIT and underscore the need for standardized diagnostic criteria.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 9","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12467063/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145173229","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":"The Incidence of IgG4-Related Disease in Slovenia-Single-Centre Experience.","authors":"Alojzija Hočevar, Aleš Grošelj, Gregor Hawlina, Matic Koželj, Andrej Škoberne, Jože Pižem, Vesna Jurčić","doi":"10.3390/biomedicines13092281","DOIUrl":"10.3390/biomedicines13092281","url":null,"abstract":"<p><p><b>Background:</b> Data on the incidence of IgG4-related disease (IgG4-RD) are scarce. Our aim was to determine the incidence of IgG4-RD in a well-defined region. Methods: This retrospective study covered the Ljubljana region over the period from January 2012 to December 2024. A review of cases diagnosed with IgG4-RD was performed at several departments of the University Medical Centre Ljubljana-an integrated secondary/tertiary university teaching hospital (rheumatology, nephrology, angiology, gastroenterology, abdominal surgery, ENT surgery, ophthalmology). While IgG4-RD cases at the Department of Rheumatology were collected prospectively, potential cases at other departments were retrieved by searching electronic medical database for the keyword \"IgG4\". In addition, the Institute of Pathology, Faculty of Medicine, University of Ljubljana, provided a list of patients with histological features consistent with IgG4-RD. Year-specific incidence rates and an average incidence rate over the 13-year period were determined. Clinical features of patients were analysed. <b>Results:</b> During the observation period, 58 cases of IgG4-RD were diagnosed. Of these, 35 patients were residents of the Ljubljana region, which had an average adult population of 541,600. The estimated average annual incidence rate of IgG4-RD was 5.0 per million (95% confidence interval: 3.5; 6.9), with year-specific incidence rates fluctuating between 1.8 and 9.3 per million adults. The cases were stratified into four phenotypic categories: pancreato-hepato-biliary (17%), retroperitoneal fibrosis-aortitis (43%), head and neck-limited (14%), and Mikulicz syndrome with systemic involvement (26%). <b>Conclusions:</b> The average annual incidence rate of IgG4-RD was 5 per million adults, with the retroperitoneal fibrosis-aortitis phenotype predominating in our cohort.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 9","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12467084/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145173106","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":"Artificial Intelligence in the Diagnosis and Treatment of Brain Gliomas.","authors":"Kyriacos Evangelou, Ioannis Kotsantis, Aristotelis Kalyvas, Anastasios Kyriazoglou, Panagiota Economopoulou, Georgios Velonakis, Maria Gavra, Amanda Psyrri, Efstathios J Boviatsis, Lampis C Stavrinou","doi":"10.3390/biomedicines13092285","DOIUrl":"10.3390/biomedicines13092285","url":null,"abstract":"<p><p>Brain gliomas are highly infiltrative and heterogenous tumors, whose early and accurate detection as well as therapeutic management are challenging. Artificial intelligence (AI) has the potential to redefine the landscape in neuro-oncology and can enhance glioma detection, imaging segmentation, and non-invasive molecular characterization better than conventional diagnostic modalities through deep learning-driven radiomics and radiogenomics. AI algorithms have been shown to predict genotypic and phenotypic glioma traits with remarkable accuracy and facilitate patient-tailored therapeutic decision-making. Such algorithms can be incorporated into surgical planning to optimize resection extent while preserving eloquent cortical structures through preoperative imaging fusion and intraoperative augmented reality-assisted navigation. Beyond resection, AI may assist in radiotherapy dose distribution optimization, thus ensuring maximal tumor control while minimizing surrounding tissue collateral damage. AI-guided molecular profiling and treatment response prediction models can facilitate individualized chemotherapy regimen tailoring, especially for glioblastomas with MGMT promoter methylation. Applications in immunotherapy are emerging, and research is focusing on AI to identify tumor microenvironment signatures predictive of immune checkpoint inhibition responsiveness. AI-integrated prognostic models incorporating radiomic, histopathologic, and clinical variables can additionally improve survival stratification and recurrence risk prediction remarkably, to refine follow-up strategies in high-risk patients. However, data heterogeneity, algorithmic transparency concerns, and regulatory challenges hamstring AI implementation in neuro-oncology despite its transformative potential. It is therefore imperative for clinical translation to develop interpretable AI frameworks, integrate multimodal datasets, and robustly validate externally. Future research should prioritize the creation of generalizable AI models, combine larger and more diverse datasets, and integrate multimodal imaging and molecular data to overcome these obstacles and revolutionize AI-assisted patient-specific glioma management.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 9","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12467936/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145172784","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":"Exploratory Analysis of Regulated Cell Death-Related Genes as Potential Prognostic Biomarkers in Endometrial Carcinoma.","authors":"Yu-Xuan Lin, Dong-Yan Cao","doi":"10.3390/biomedicines13092289","DOIUrl":"10.3390/biomedicines13092289","url":null,"abstract":"<p><p><b>Objective:</b> This study aims to explore the mechanism of regulated cell death-related genes in the development of endometrial carcinoma. <b>Methods:</b> Endometrial carcinoma-related datasets were yielded via the Cancer Genome Atlas and Gene Expression Omnibus databases, and regulated cell death-related genes were extracted from the literature. Differential expression analysis, weighted gene co-expression network analysis, and protein interaction analysis were performed to identify critical regulated cell death-related genes. Gene set enrichment analysis was used to identify the functional pathways involved in these critical genes. Afterward, the best clustering approach for tumor samples was yielded via consensus clustering analysis, and nomogram prediction models were built. Shiny Methylation Analysis Resource Tool was used to compare the expression levels of CpG methylation probes for critical genes between tumor and normal samples. Spearman correlation analysis was conducted to investigate the relationship between critical genes and various immune features. Eventually, immuno-infiltrative analysis was implemented, and potential therapeutic agents were screened targeting critical genes. The data were analyzed and visualized by R software using different packages. In addition, the expressions of critical genes were validated by quantitative real-time polymerase chain reaction and immunochemistry. <b>Results:</b> Four critical genes, namely <i>GBP2</i>, <i>SLC11A1</i>, <i>P2RX7</i>, and <i>HCLS1</i>, were identified, and they were involved in various functional pathways such as leukocyte-mediated cytotoxicity. There were substantial differences in CpG methylation in <i>GBP2</i>, <i>SLC11A1</i>, and <i>HCLS1</i> between tumor and normal samples. As for immune features, all critical genes were positively connected with immunosuppressive factors such as TIGIT and most HLA molecules in endometrial carcinoma. The critical genes high/low expression groups of tumor samples showed different immune responses towards PD-1, PD-L1, and CTLA-4 immunotherapy. The infiltration of 24 immune cells, such as effector memory CD8 T cells, was notably different between tumor and normal samples. Based on sensitivity analysis of chemotherapeutic agents, we found the highest positive correlation between <i>SLC11A1</i> and \"BI.2536\" and the strongest passive correlation of <i>HCLS1</i> and <i>GBP2</i> with \"Ribociclib\", as well as <i>P2RX7</i> with \"BMS.754807\". Quantitative real-time polymerase chain reaction suggested that the expression trends of <i>GBP2</i>, <i>P2RX7</i>, and <i>HCLS1</i> were consistent with the results of bioinformatic analysis. <b>Conclusions:</b> Regulated cell death-related genes (<i>GBP2</i>, <i>SLC11A1</i>, <i>P2RX7</i>, and <i>HCLS1</i>) may play a role in endometrial carcinoma development, which can provide new ideas for the treatment and prognosis prediction of this disease.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 9","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12467941/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145173003","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":"Recent Advances in Parkinson's Disease Research: From Pathophysiology to Novel Therapeutic Approaches.","authors":"Sujung Yeo","doi":"10.3390/biomedicines13092283","DOIUrl":"10.3390/biomedicines13092283","url":null,"abstract":"<p><p>Parkinson's disease is a progressive neurodegenerative disorder affecting approximately 1-2% of the population over 65 years of age [...].</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 9","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12466970/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145173252","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":"Clopidogrel Influences Fracture Healing Under Ischemic Conditions.","authors":"Sebastian Schreiber, Janine Stutz, Lukas Keller, Wolfgang Metzger, Tobias Fritz, Christian Schönbeck, David Osche, Marcus Örgel, Michael D Menger, Tim Pohlemann, Emmanouil Liodakis, Matthias W Laschke, Marcel Orth","doi":"10.3390/biomedicines13092286","DOIUrl":"10.3390/biomedicines13092286","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Patients suffering from fractures are often treated with clopidogrel during the phase of bone healing due to multiple comorbidities. Studies indicate that clopidogrel suppresses osteoblast proliferation and the formation of trabecular bone. However, it is unknown whether clopidogrel also affects fracture healing under ischemic conditions, as they may occur in multimorbid patients. <b>Methods</b>: To test this in the present study, a murine ischemia model was performed in CD-1 mice by ligating the right deep femoral artery to induce mild ischemia of the right lower limb. A closed fracture of the femur was then stabilized by inserting an intramedullary lag screw. The animals received either 3 mg/kg body weight clopidogrel daily per os or vehicle (control). Bone healing was assessed by biomechanical, radiological, histomorphometrical and Western blot analyses 2 and 5 weeks postoperatively. <b>Results</b>: The fractured femurs in the clopidogrel group exhibited no increase in biomechanical stiffness throughout the observation period in contrast to controls. While the radiological analysis showed no differences between both groups, histomorphometric analyses demonstrated a significantly reduced bridging score, less bone and more connective tissue within the callus of clopidogrel-treated animals. Western blot analyses revealed a significantly reduced expression of the osteogenic marker bone morphogenetic protein (BMP)-4 and an increased expression of the blood vessel marker CD31. <b>Conclusions</b>: These results show that clopidogrel may impair fracture healing under challenging ischemic conditions, which is associated with a shift in angiogenic and osteogenic expression markers in the callus tissue. Therefore, clopidogrel treatment may not be recommended in fracture patients with tissue ischemia.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 9","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12467816/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145172954","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}