Biomedicines最新文献

{"title":"Real-World Effectiveness and Safety of Anti-CGRP Monoclonal Antibodies in the Prevention of High-Frequency Episodic and Chronic Migraine in Romania-A Multicenter Retrospective Observational Study.","authors":"Alin Ciubotaru, Albert Vamanu, Cristina Grosu, Victor Constantinescu, Emilian Bogdan Ignat, Laura-Elena Cucu, Daniel Alexa, Alexandra Mastaleru, Bogdan Ionut Pana, Florina Antochi, Adina Maria Roceanu","doi":"10.3390/biomedicines14092125","DOIUrl":"10.3390/biomedicines14092125","url":null,"abstract":"<p><p><b>Background:</b> Real-world evidence regarding the effectiveness and safety of anti-calcitonin gene-related peptide (CGRP) monoclonal antibodies in Eastern European populations remains limited. We aimed to evaluate treatment outcomes and safety in Romanian patients with high-frequency episodic migraine (HFEM) and chronic migraine (CM). <b>Methods:</b> We conducted a multicenter retrospective observational cohort study including 113 adults with HFEM (<i>n</i> = 38) or CM (<i>n</i> = 75) who initiated treatment with galcanezumab, erenumab, fremanezumab, or eptinezumab at specialized headache centers in Romania. Monthly migraine days (MMDs) in HFEM and monthly headache days (MHDs) in CM were assessed at the baseline and during follow-up. Treatment outcomes, discontinuation, persistence, and adverse events were evaluated during routine clinical follow-up. <b>Results:</b> At month 6, headache frequency was substantially reduced in both groups, with median MMDs decreasing from 10 to 2 in patients with HFEM and median MHDs decreasing from 25 to 6 in patients with CM. A ≥50% reduction in headache frequency was achieved by 78.9% of patients with HFEM and 64.0% of those with CM. Among the patients with CM, 70.7% met the predefined criterion for conversion to episodic migraine at month 6. During follow-up, 22 patients discontinued treatment. Adverse events were reported in 28 patients (24.8%), were predominantly non-serious, and resulted in treatment discontinuation in 3 patients (2.7%). No serious adverse events were documented. Treatment persistence at 12 months was 82.3%. <b>Conclusions:</b> In this Romanian real-world cohort, anti-CGRP monoclonal antibody treatment was associated with substantial reductions in migraine/headache frequency in patients with HFEM and CM. The treatment was generally well-tolerated, with predominantly non-serious adverse events and a low rate of discontinuation due to adverse events. These findings provide real-world evidence from Romania and support further prospective evaluation of the long-term effectiveness and safety of anti-CGRP monoclonal antibodies.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"14 9","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13604649/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149057560","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":"Multi-Omics Analysis Identifies TTYH3 and MPG as Candidate Osteoporosis-Associated Biomarkers in Osteoblasts and Characterizes Spatial Heterogeneity of SPP1 in the Osteoporotic Bone Microenvironment.","authors":"Hengyi Diao, Qianning Li, Yucheng Tu, Yang Wu, Qiaojun Huang, Fangang Meng, Weishen Chen","doi":"10.3390/biomedicines14092126","DOIUrl":"10.3390/biomedicines14092126","url":null,"abstract":"<p><p><b>Background</b>: Osteoporosis (OP) arises from dysregulated bone metabolism driven by genetic and epigenetic factors. Osteoblasts are central to bone formation, and their functional heterogeneity-shaped by genetic background and receptor expression profiles-may critically influence OP susceptibility. This study aimed to identify osteoblast-specific genes robustly associated with OP and elucidate their underlying pathogenic mechanisms. <b>Methods</b>: We analyzed single-cell RNA sequencing (scRNA-seq), bulk RNA sequencing (bulk RNA-seq), and spatial transcriptomics (ST) datasets of osteoblasts. Differentially expressed genes (DEGs) were identified from scRNA-seq and bulk RNA-seq datasets, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Three machine learning methods and an artificial neural network (ANN)-based weighting analysis, together with weighted gene co-expression network analysis (WGCNA), were used to prioritize candidate OP-associated genes. ST data were integrated with CellChat analysis based on scRNA-seq data to investigate spatial expression patterns and potential cell-cell communication. Candidate genes were validated by immunohistochemical staining in human femoral head samples and quantitative real-time PCR (qRT-PCR) in MC3T3-E1 cells. <b>Results</b>: The intersecting DEGs from the scRNA-seq and bulk RNA-seq datasets were potentially related to inhibition of ossification. Three machine learning methods identified five osteoporosis-associated candidate genes: TTYH3, NRBP2, MPG, HSPG2, and GPR153, which were subsequently evaluated using ANN-based weighting analysis. Among these, TTYH3 and MPG were identified as OP-related genes by WGCNA. Integration of the scRNA-seq, ST, and CellChat results suggested that SPP1 was highly expressed in osteoblasts from the OP sample and exhibited a spatially heterogeneous expression pattern. Immunohistochemical staining of human femoral head tissues from individuals with normal bone mass and osteoporosis, together with qRT-PCR analysis in MC3T3-E1 cells, further validated the differential expression of TTYH3 and MPG. <b>Conclusions</b>: This study identified candidate osteoporosis-associated biomarkers and provided insights into potential pathogenic mechanisms, thereby establishing a basis for future mechanistic and clinical validation.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"14 9","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13604504/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149057914","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":"Plasma Metabolomic Alterations Are Associated with T-Cell Senescence, Cytokine Dysregulation, and Prognosis in Elderly COVID-19 Patients.","authors":"Ying Shang, Hui Zhang, Yinan Lang, Tingting Hu, Chun Chang, Liuyang Zhang","doi":"10.3390/biomedicines14092118","DOIUrl":"10.3390/biomedicines14092118","url":null,"abstract":"<p><p><b>Background</b>: Elderly patients with COVID-19 are at increased risk of severe disease and mortality. Interactions between the plasma metabolome and the immune microenvironment may influence disease progression and outcomes; however, the associations of metabolic alterations with T-cell senescence, cytokine dysregulation, and clinical outcomes in this population remain poorly understood. <b>Methods:</b> Plasma metabolomic profiling was performed in elderly COVID-19 patients and healthy controls to identify differential metabolites and metabolic features associated with clinical outcomes. Machine learning approaches were applied to identify key metabolic features associated with 180-day mortality. Correlation analyses were performed to evaluate the associations of metabolic alterations with T-cell senescence and cytokine profiles. In vitro experiments were further performed to evaluate the effects of lysophosphatidylethanolamine (LPE) on T-cell senescence. <b>Results:</b> Plasma metabolomic profiles differed markedly between elderly COVID-19 patients and healthy controls. Distinct metabolic alterations were also observed between non-survivors and survivors, with phosphatidylethanolamine (PE) 36:3, glycochenodeoxycholic acid, and deoxycholic acid showing higher levels in non-survivors. Machine learning identified 24 key metabolites associated with 180-day mortality, primarily involving bile acid metabolism, fatty acid oxidation, and phospholipid metabolism. Dysregulated plasma phospholipid metabolism, particularly involving phosphatidylcholine (PC), lysophosphatidylcholine (LPC), phosphatidylethanolamine (PE), and lysophosphatidylethanolamine (LPE), was associated with T-cell senescence in elderly COVID-19 patients. Moreover, exogenous LPE 18:1 attenuated selected markers of T-cell senescence in vitro. Additionally, five cytokines-GRO-α, IL-6, IL-8, IP-10, and TSLP-showed higher levels in non-survivors. Metabolic alterations were associated with inflammatory cytokine profiles, particularly IP-10 and TSLP, while deoxycholic acid showed concurrent associations with IL-6, IP-10, and IL-8. <b>Conclusions:</b> Plasma metabolomic alterations were associated with T-cell senescence, inflammatory cytokine profiles, and clinical outcomes in elderly patients with COVID-19.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"14 9","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13604901/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149057997","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":"Factors Associated with Invasive Mechanical Ventilation Requirement in Older ICU Patients: The Roles of Frailty, Comorbidity, and Acute Illness Severity.","authors":"Maşallah Çakırer, Ahmet Düzgün","doi":"10.3390/biomedicines14092113","DOIUrl":"10.3390/biomedicines14092113","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Invasive mechanical ventilation (IMV) in older intensive care unit (ICU) patients represents a critical turning point in disease trajectory. While acute illness severity is a key determinant of IMV, the independent contributions of frailty and comorbidity remain uncertain. This study evaluated whether integrating geriatric domains with acute physiological parameters provides additional information about the risk of IMV requirement, beyond acute severity alone. <b>Methods</b>: In this single-center retrospective cohort study, patients aged ≥65 years admitted to a tertiary ICU between January 2024 and December 2025 were included. Variables obtained within the first 24 h included Clinical Frailty Scale (CFS), Charlson Comorbidity Index (CCI), Sequential Organ Failure Assessment (SOFA), Acute Physiology and Chronic Health Evaluation II (APACHE II), and laboratory parameters. The primary outcome was IMV requirement. Multivariable logistic regression models were constructed, and performance was assessed using discrimination (AUC) and calibration. <b>Results</b>: Among 285 patients (median age 77 years [IQR 71-86]), 161 (56.5%) required IMV. These patients had higher frailty, comorbidity burden, and illness severity on univariable comparison. In multivariable analysis, SOFA score showed the strongest independent association with IMV requirement (adjusted OR 1.91; 95% CI 1.63-2.23; <i>p</i> < 0.001), followed by serum lactate (adjusted OR 1.30; 95% CI 1.08-1.58; <i>p</i> = 0.006). Older age was independently associated with lower odds of IMV (adjusted OR 0.96 per year; 95% CI 0.92-1.00; <i>p</i> = 0.034). Neither frailty (CFS) nor comorbidity burden (CCI) remained independently associated after adjustment. The final SOFA- and APACHE II-based models demonstrated AUCs of 0.899 (95% CI 0.864-0.933) and 0.911 (95% CI 0.879-0.944), respectively. <b>Conclusions</b>: Acute organ dysfunction and early lactate remain the dominant determinants of IMV requirement in older ICU patients. Neither comorbidity burden nor frailty retained an independent association once acute severity was accounted for; instead, advancing age was independently associated with a lower likelihood of IMV, a finding that may reflect unmeasured treatment-limitation decisions and warrants further investigation. These findings suggest that frailty and comorbidity indices should not be used in isolation as triggers for ventilatory decision-making and instead support a framework centered on acute severity and perfusion markers, with age considered mainly as a marker of care-goal context.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"14 9","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13604124/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149058036","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":"CDELDA: A Content-Based Dual-Encoder for Cold-Start lncRNA-Disease Association Prediction.","authors":"Sanguk Kim, Taehyeon Yun, Jihwan Ha","doi":"10.3390/biomedicines14092121","DOIUrl":"10.3390/biomedicines14092121","url":null,"abstract":"<p><p><b>Background/Objectives:</b> An important challenge in long non-coding RNA (lncRNA)-disease association prediction is prioritizing candidates when neither target node has association records in the training data, even though content features are available. This study aimed to develop and evaluate a content-based model for this both-cold setting. <b>Methods:</b> We developed CDELDA, a dual-encoder model combining lncRNA sequence, structure, and expression features with disease text, semantic similarity, and ontology-structure features. CDELDA was compared with five baseline methods on a normalized benchmark comprising 1662 lncRNAs, 220 diseases, and 9920 positive associations. Evaluation covered warm, lncRNA-cold, disease-cold, and both-cold settings, with association-derived inputs constructed from training labels. Disease-macro area under the receiver operating characteristic curve (AUROC) was the main comparison metric, complemented by average precision and top-ranked retrieval metrics. Feature ablation, disease-feature perturbation, sensitivity analyses, and literature-based case studies further characterized model performance. <b>Results:</b> Under both-cold evaluation, CDELDA achieved a mean disease-macro AUROC of 0.6617, compared with 0.6123 for SIMCLDA, the highest-scoring literature baseline on this metric. Relative performance varied across evaluation settings and metrics. Removing expression features produced the largest decrease in disease-macro AUROC among individual lncRNA feature removals. Reassigning disease features reduced performance, although ranking performance was partly retained. Literature review identified functional or observational support for 14 of 20 reviewed candidate pairs. <b>Conclusions:</b> These findings suggest that CDELDA can support content-based candidate prioritization under both-cold evaluation. The predictions provide candidates for biological follow-up, with disease-specific relevance requiring independent validation.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"14 9","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13604804/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149057907","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":"Transposon Vectors Enable Accelerated Development of Cellular Assay Platforms for the Identification and Characterization of Anti-Viral Small-Molecule Cell-Entry Inhibitors and Neutralizing Antibodies.","authors":"Mona Pißarreck, Kristina Katsoutas, Celina Lea Kinder, Jörn Stitz","doi":"10.3390/biomedicines14092119","DOIUrl":"10.3390/biomedicines14092119","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Screening for neutralizing antibodies (nAbs) or antiviral small-molecule inhibitors (SMIs) using live virus is laborious and often confined to higher biosafety levels, thus restricting accessibility. The use of murine leukemia virus (MLV)-derived pseudotype vector particles displaying spike or envelope proteins of the targeted human pathogen and susceptible target cells expressing the cognate virus receptor lowers biosafety requirements. Extended drug discovery campaigns demand larger quantities of pseudotype vector particles most favorably produced by stable high-titer suspension vector-producing cells (SVPCs). We aimed to demonstrate that this can be achieved by employing transposon vectors. <b>Methods</b>: <i>Sleeping Beauty</i> transposon vectors were used to rapidly establish MLV-derived SVPCs using two SARS-CoV-2 spike variants as well as highly susceptible target cells expressing the virus receptor ACE2 and the cellular protease TMPRSS2. Generated cell lines and viral vectors were characterized by employing syncytial-formation assay, Western blot analysis, vector titration and neutralization experiments using two SMIs and two nAbs. <b>Results</b>: The expression, fusogenicity and particle incorporation of two spike variants was confirmed and the production of high-titer MLV(SARS-CoV-2) particles was demonstrated. The components of this novel cellular assay platform consisting of stable susceptible target cells and high-yield SVPCs were successfully utilized to characterize nAbs directed against the spike protein and cell-entry-inhibiting SMIs targeting the cellular protease TMPRSS2. <b>Conclusions</b>: The proof-of-concept (POC) cellular assay platform components, namely, the two SVPCs and the highly susceptible target cell line, should prove useful in future small-molecule cell-entry inhibitor discovery campaigns, as well as the development of neutralizing antibodies and vaccine candidates directed against SARS-CoV-2. Moreover, the panel of transposon vectors should be easily adaptable to other non-cytotoxic viral pathogens provided these efficiently pseudotype MLV.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"14 9","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13604224/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149058081","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":"Development of Novel Prenatal Prediction Models for Birth-Weight Estimation in Low-Risk Third-Trimester Pregnancies.","authors":"Sevda Yelec, Rauf Melekoglu, Yusuf Kemal Arslan, Cihan Cetin, Selim Buyukkurt, Gulsah Seydaoglu","doi":"10.3390/biomedicines14092122","DOIUrl":"10.3390/biomedicines14092122","url":null,"abstract":"<p><p><b>Objective:</b> Sonographic evaluation of the fetus and estimation of fetal weight are integral components of modern obstetric practice. Estimated fetal weight (EFW) plays a crucial role in predicting macrosomia, diagnosing intrauterine growth restriction, and monitoring fetal development. This study aimed to improve birth-weight prediction in low-risk term pregnancies by combining conventional fetal biometry with maternal anthropometry and selected fetal soft-tissue and cardiac measurements. <b>Materials and Methods:</b> In 94 low-risk, term singleton pregnancies scheduled for elective cesarean delivery, standardized prenatal ultrasound was performed within 24 h before birth by a single operator. Neonatal anthropometry was obtained within 6 h postnatally. Multiple linear regression was used to develop conventional and extended prenatal birth-weight prediction models with actual birth weight as the dependent variable, and their performance was compared with Hadlock EFW. <b>Results:</b> Mean actual birth weight was 3178.9 ± 359.5 g and mean Hadlock EFW was 3201.6 ± 399.7 g. Hadlock estimation correlated strongly with birth weight (r = 0.826) and had a mean absolute error (MAE) of 181.0 g. Abdominal circumference was the strongest conventional sonographic correlate of birth weight. The conventional prenatal Model 2 achieved R² = 0.710 and MAE = 150.1 g. The extended prenatal Model 5, which combined conventional biometry with symphysis-fundal height, femoral soft-tissue thickness, right atrial area, maternal abdominal fat thickness, and aortic valve diameter, showed the best performance (R² = 0.783; MAE = 133.2 g). Its optimism-corrected and repeated cross-validated R² values were 0.739 and 0.725, respectively. <b>Conclusions:</b> The newly proposed formulas, particularly Model 5, demonstrated better internally validated predictive performance than the Hadlock baseline in this cohort, suggesting that the integration of selected maternal anthropometric and additional fetal ultrasonographic measurements with conventional biometry may improve birth-weight estimation. These findings warrant external validation in larger and more diverse populations prior to clinical implementation.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"14 9","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13604655/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149057793","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":"Safety of Biologic Therapy for Inflammatory Bowel Disease in Liver Transplant Recipients.","authors":"Tanja Elger, Johanna Loibl, Martina Müller, Sophia Rusch, Lucia Baier-Kleinhenz, Arne Kandulski, Christa Buechler, Hauke Christian Tews","doi":"10.3390/biomedicines14092117","DOIUrl":"10.3390/biomedicines14092117","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Liver diseases and chronic inflammatory bowel diseases (IBD) are closely associated, particularly primary sclerosing cholangitis (PSC) and ulcerative colitis (UC). In severe cases of PSC, liver transplantation (LT) may be required, just as severe IBD may necessitate biologic therapy. Evidence on combining biologics with post-transplant immunosuppression is limited, particularly regarding hepatotoxicity, infections, and drug-drug interactions. We therefore assessed the safety of biologic therapy for IBD in LT recipients. <b>Methods</b>: In this retrospective, single-center analysis, all patients treated at the inflammatory bowel disease and post-liver transplantation outpatient clinics of the University Hospital Regensburg were screened. Patients with both LT and IBD were included in the analysis. Medical records, laboratory parameters, and imaging studies were reviewed. <b>Conclusions</b>: A total of 17 liver transplant recipients with IBD were identified. Eleven patients had PSC as the underlying liver disease, while the remaining patients had autoimmune hepatitis (AIH), PSC-AIH overlap syndrome, or cryptogenic liver cirrhosis. Three patients had Crohn's disease, and 14 had ulcerative colitis. Five patients required biologic therapy because of active IBD. Two patients received two sequential biologic agents, whereas one patient received four different biologics during follow-up. No significant safety signals were observed regarding hepatotoxicity, susceptibility to infections, or interactions with concomitant immunosuppressive therapy, including tacrolimus, mycophenolate mofetil, ciclosporin, and prednisolone. No evidence of clinically relevant safety concerns associated with biologic therapy was identified in liver transplant recipients with IBD. Therefore, biologic therapy combined with conventional post-transplant immunosuppression appears feasible and well tolerated in LT recipients with active IBD; larger prospective studies are needed. However, larger prospective studies are needed to confirm these findings.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"14 9","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13604667/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149058007","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":"Immune and Redox Responses of <i>Galleria mellonella</i> to Caffeic Acid: Concentration- and Time-Dependent Patterns.","authors":"Fatih Battal, Serhat Kaya","doi":"10.3390/biomedicines14092116","DOIUrl":"10.3390/biomedicines14092116","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Caffeic acid is a naturally occurring phenolic compound with antioxidant and immunomodulatory properties, but its integrated effects on innate immune and redox-related physiology in <i>Galleria mellonella</i> remain unclear. This study evaluated concentration- and time-related effects of caffeic acid on immune and biochemical endpoints. <b>Methods:</b> Last-instar larvae were exposed to 0.1-5 mg/mL caffeic acid, with 20% ethanol as the vehicle comparator. Total hemocyte count (THC), Sephadex A-25 bead encapsulation, and melanization were assessed as immune endpoints; bead responses were evaluated at 4 and 24 h using independent cohorts. Total protein, superoxide dismutase (SOD), catalase (CAT), and malondialdehyde (MDA) were measured at 24 h. Experimental run was included as a fixed blocking factor in the primary inferential models; THC and biochemical endpoints were analyzed using endpoint-appropriate run-adjusted linear or rank-based models, whereas encapsulation and melanization were analyzed using ordinal and binomial generalized estimating equations (GEEs), respectively; <i>n</i> = 16 larvae per treatment for each endpoint. <b>Results:</b> THC increased significantly only at 0.5 mg/mL relative to the vehicle. Encapsulation showed a significant treatment × time interaction; all concentrations shifted encapsulation toward higher categories at 4 h, whereas 2.5 and 5 mg/mL shifted toward lower categories at 24 h. Melanization showed no significant treatment × time interaction; only 2.5 mg/mL increased melanization odds at 4 h, with no treatment-vehicle differences at 24 h. CAT increased at 2.5 and 5 mg/mL, and SOD at 2.5 mg/mL. MDA and total protein showed overall heterogeneity without significant individual treatment-vehicle differences. <b>Conclusions:</b> Caffeic acid produced non-uniform, endpoint-specific modulation of immune and antioxidant responses, with temporal dependence most evident in encapsulation.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"14 9","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13604758/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149057897","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":"Evaluation of Spontaneous Pain in a Monosodium Iodoacetate-Induced Mouse Model of Osteoarthritis Using the Mouse Grimace Scale.","authors":"Mohammed Alnoud, Jose Rios, Megan W Szobody, Ayesha A Usman, Alma Rodriguez, Thao-April Nguyen, Seryna Ayala, Ayaan S Quraishi, Massimo Salinas, Khalid Benamar","doi":"10.3390/biomedicines14092114","DOIUrl":"10.3390/biomedicines14092114","url":null,"abstract":"<p><p>Animal models are critical for elucidating disease mechanisms and pathological outcomes, and for evaluating therapeutic interventions. Osteoarthritis (OA) is a leading cause of chronic pain and disability globally. Clinically, individuals with OA experience both sensory and ongoing pain. However, ongoing pain, as assessed by the Mouse Grimace Scale (MGS), has not yet been evaluated in animal models of OA. This study aims to address this significant knowledge gap. We induced OA by intra-articular injection of monosodium iodoacetate (MIA), while control mice received saline injections. We assessed pain behaviors using the MGS on days 1, 3, 7, and 14 after MIA administration. MIA-treated mice exhibited significantly higher MGS scores than saline-treated controls throughout the study period, indicating ongoing pain-related behavior in the MIA OA model. Furthermore, longitudinal studies showed that this pain is chronic, as seen in people with OA. These findings support the usefulness of the MGS test in the MIA model for studying ongoing pain.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"14 9","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13604891/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149057885","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}