Biomedicines

16 pages, 2928 KB

Open AccessArticle

Immunomodulatory Potential of a Composite Amniotic Membrane Hydrogel for Wound Healing: Effects on Macrophage Cytokine Secretion

by Tao Wang, Zhiyuan Zhu, Wei Hua and Siliang Xue

Biomedicines 2025, 13(10), 2574; https://doi.org/10.3390/biomedicines13102574 - 21 Oct 2025

Cited by 1 | Viewed by 581

Abstract

Background: The human acellular amniotic membrane (HAAM) is widely used as a decellularized bioscaffold in tissue engineering to promote wound healing, but its clinical application is limited by poor mechanical properties, rapid degradation, and handling difficulties. This study aimed to develop a modified [...] Read more.

Background: The human acellular amniotic membrane (HAAM) is widely used as a decellularized bioscaffold in tissue engineering to promote wound healing, but its clinical application is limited by poor mechanical properties, rapid degradation, and handling difficulties. This study aimed to develop a modified amniotic membrane-based composite material loaded with vascular endothelial growth factor (VEGF) and the Notch signaling inhibitor N-[N-(3,5-difluorophenacetyl)-Lalanylhydrazide]-Sphenylglycine t-butyl ester (DAPT) to enhance wound healing by modulating macrophage polarization and cytokine secretion. Methods: VEGF-loaded gellan gum-hyaluronic acid (GG-HA) hydrogels (VEGF-GG-HA) and DAPT-loaded HAAM (DAPT-HAAM) were prepared and combined to form a novel composite material (VEGF-GG-HA & DAPT-HAAM). The morphology and microstructure of the materials were characterized using scanning electron microscopy. In vitro studies were conducted using the human monocytic cell line (Tohoku Hospital Pediatrics-1, THP-1) to evaluate the effects of the materials on cell viability, cytokine secretion, and protein expression. Assessments included CCK-8 assays, ELISA, quantitative real-time PCR, Western blot analysis, and immunohistochemical staining. Results: The composite material VEGF-GG-HA & DAPT-HAAM exhibited good biocompatibility and significantly promoted THP-1 cell proliferation compared to control and single-component groups. It enhanced the secretion of IL-10, TNF-α, TGF-β, MMP1, and MMP3, while suppressing excessive TGF-β overexpression. The material also modulated macrophage polarization, showing a trend toward anti-inflammatory M2 phenotypes while maintaining pro-inflammatory signals (e.g., TNF-α) for a balanced immune response. Conclusions: The modified amniotic membrane hydrogel composite promotes wound healing through a phased immune response: it modulates macrophage polarization (balancing M1 and M2 phenotypes), enhances cytokine and matrix metalloproteinase secretion, and controls TGF-β levels. These effects contribute to improved vascular remodeling, reduced fibrosis, and prevention of scar formation, demonstrating the potential for enhanced wound management. Full article

(This article belongs to the Special Issue New Advances in Wound Healing and Skin Regeneration)

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21 pages, 1703 KB

Open AccessArticle

Beyond Biomarkers: Blending Copeptin and Clinical Cues to Distinguish Central Diabetes Insipidus from Primary Polydipsia in Children

by Diana-Andreea Ciortea, Carmen Loredana Petrea (Cliveți), Gabriela Isabela Verga (Răuță), Sorin Ion Berbece, Gabriela Gurău, Silvia Fotea and Mădălina Nicoleta Matei

Biomedicines 2025, 13(10), 2573; https://doi.org/10.3390/biomedicines13102573 - 21 Oct 2025

Viewed by 683

Abstract

Background: Polyuria–polydipsia syndrome (PPS) in children poses a major diagnostic challenge, as central diabetes insipidus (CDI) and primary polydipsia (PP) require distinct treatments. Although copeptin is a robust diagnostic biomarker, using only fixed thresholds may not adequately support decision making in borderline [...] Read more.

Background: Polyuria–polydipsia syndrome (PPS) in children poses a major diagnostic challenge, as central diabetes insipidus (CDI) and primary polydipsia (PP) require distinct treatments. Although copeptin is a robust diagnostic biomarker, using only fixed thresholds may not adequately support decision making in borderline cases. To address this gap, we evaluated a multimodal diagnostic approach that integrates copeptin dynamics with clinical profiling. Methods: In a prospective diagnostic study (2019–2025), 24 children with PPS (CDI = 11, PP = 13) underwent hypertonic saline testing with serial sodium, osmolality, and copeptin sampling. Predictors included stimulated copeptin, peak sodium, peak osmolality, test duration, and tolerability. A Ridge regression model was applied and internally validated with stratified cross-validation. Results: Stimulated copeptin was the strongest discriminator, while sodium/osmolality dynamics and tolerability provided complementary value. The multimodal model achieved cross-validated AUC of 0.937 with 83.3% accuracy, and the procedure was safe and feasible in children. These findings support moving beyond biomarker cut-offs toward integrative diagnostic approaches that better reflect real-world clinical practice. Conclusions: Combining copeptin with clinical profiling in a penalized regression framework yields a robust and interpretable tool for distinguishing CDI from PP. More broadly, such integrative models may enhance diagnostic precision in rare pediatric disorders and provide a foundation for future multicenter validation and clinical decision-support applications. Full article

(This article belongs to the Section Molecular and Translational Medicine)

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3 pages, 150 KB

Open AccessEditorial

From Stress Pathways to Space Biology: An Odyssey in Molecular and Translational Medicine

by Alkmini T. Anastasiadi and Vassilis L. Tzounakas

Biomedicines 2025, 13(10), 2572; https://doi.org/10.3390/biomedicines13102572 - 21 Oct 2025

Viewed by 353

Abstract

Nowadays, molecular and translational medicine can be seen as a journey across vast and sometimes challenging landscapes of discovery [...] Full article

(This article belongs to the Special Issue State-of-the-Art and Novel Approaches in Molecular and Translational Medicine in Europe)

21 pages, 3605 KB

Open AccessArticle

Brain Tumor Classification in MRI Scans Using Edge Computing and a Shallow Attention-Guided CNN

by Niraj Anil Babar, Junayd Lateef, ShahNawaz Syed, Julia Dietlmeier, Noel E. O’Connor, Gregory B. Raupp and Andreas Spanias

Biomedicines 2025, 13(10), 2571; https://doi.org/10.3390/biomedicines13102571 - 21 Oct 2025

Viewed by 886

Abstract

Background/Objectives: Brain tumors arise from abnormal, uncontrolled cell growth due to changes in the DNA. Magnetic Resonance Imaging (MRI) is vital for early diagnosis and treatment planning. Artificial intelligence (AI), especially deep learning, has shown strong potential in assisting radiologists with MRI analysis. [...] Read more.

Background/Objectives: Brain tumors arise from abnormal, uncontrolled cell growth due to changes in the DNA. Magnetic Resonance Imaging (MRI) is vital for early diagnosis and treatment planning. Artificial intelligence (AI), especially deep learning, has shown strong potential in assisting radiologists with MRI analysis. However, many brain tumor classification models achieve high accuracy at the cost of large model sizes and slow inference, limiting their practicality for medical edge computing. In this work we introduce a new attention-guided classification model and explore how model parameters can be reduced without significantly impacting accuracy. Methods: We develop a shallow attention-guided convolutional neural network (ANSA_Ensemble) and evaluate its effectiveness using Monte Carlo simulations, ablation studies, cross-dataset generalization, and Grad-CAM-generated heatmaps. Several state-of-the-art model compression techniques are also applied to improve the efficiency of our classification pipeline. The model is evaluated on three open-source brain tumor datasets. Results: The proposed ANSA_Ensemble model achieves a best accuracy of 98.04% and an average accuracy of 96.69 ± 0.64% on the Cheng dataset, 95.16 ± 0.33% on the Bhuvaji dataset, and 95.20 ± 0.40% on the Sherif dataset. Conclusions: The performance of the proposed model is comparable to state-of-the-art methods. We find that the best tradeoff between accuracy and speed-up factor is consistently achieved using depthwise separable convolutions. The ablation study confirms the effectiveness of the introduced attention blocks and shows that model accuracy improves as the number of attention blocks increases. Our code is made publicly available. Full article

(This article belongs to the Special Issue Advances in Brain Tumor Diagnosis: Innovations and Emerging Technologies)

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15 pages, 717 KB

Open AccessArticle

A Retrospective Study Regarding the Implementation of Laparoscopy in Colon Cancer Through the Evaluation of Lymph Node Yield and Oncological Safety Margins in a Medium-Volume Center in Eastern Europe

by Iulian Slavu, Raluca Tulin, Alexandru Dogaru, Ileana Dima, Cristina Orlov Slavu, Marius Popescu, Bogdan Nitescu, Daniela-Elena Gheoca Mutu and Adrian Tulin

Biomedicines 2025, 13(10), 2570; https://doi.org/10.3390/biomedicines13102570 - 21 Oct 2025

Viewed by 527

Abstract

Background: Laparoscopic surgical procedures are increasingly adopted for colorectal cancer because of their advantages in perioperative outcomes. However, their implementation in medium-volume centers (<50 laparoscopic resections per year) remains limited. Methods: A retrospective study was conducted on 274 patients undergoing colorectal cancer surgery [...] Read more.

Background: Laparoscopic surgical procedures are increasingly adopted for colorectal cancer because of their advantages in perioperative outcomes. However, their implementation in medium-volume centers (<50 laparoscopic resections per year) remains limited. Methods: A retrospective study was conducted on 274 patients undergoing colorectal cancer surgery between January 2021 and June 2025. Of these, 71 (25.91%) underwent laparoscopic surgical procedures (LS) and 203 (74.09%) open surgical procedures (OS). Primary and secondary endpoints included lymph node yield, resection margin distance, tumor stage, and hospital stay. Results: The mean lymph node yield was significantly higher in the open surgical procedure group (19.74 ± 10.63) compared to the laparoscopic group (16.09 ± 5.71, p < 0.05). Patients with significant cardiopulmonary disease or prior abdominal surgery were more often directed to open surgery, introducing selection bias that may explain differences in lymph node yield and hospital stay independent of surgical technique. The resection margin distance was significantly greater in laparoscopic cases (5.68 ± 3.12 mm) than in open procedures (4.76 ± 4.47 mm, p < 0.01). Hospital stay was significantly shorter in the laparoscopic group (7.14 ± 2.32 days) compared to the open group (13.17 ± 6.76 days, p < 0.001). A statistically significant difference in tumor staging was also observed between surgical approaches (p < 0.01), with earlier-stage tumors more likely treated laparoscopically. Conclusions: In a medium-volume center, laparoscopic surgical procedures provided comparable oncologic outcomes and superior perioperative benefits relative to open surgery, despite being more frequently performed for early-stage tumors. These findings support the safe adoption of laparoscopic colectomy outside high-volume academic settings, provided appropriate case selection and technical standards are maintained. Full article

(This article belongs to the Section Cancer Biology and Oncology)

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85 pages, 19886 KB

Open AccessReview

In Vivo Models of Cardiovascular Disease: Drosophila melanogaster as a Genetic Model of Congenital Heart Disease

by Theodora M Stougiannou, Maria Koutini, Fotios Mitropoulos and Dimos Karangelis

Biomedicines 2025, 13(10), 2569; https://doi.org/10.3390/biomedicines13102569 - 21 Oct 2025

Viewed by 1034

Abstract

Drosophila melanogaster (D. melanogaster) has been widely used in biology, including classical genetics, for almost a century. With the entire D. melanogaster genome sequenced and the existence of transgenic and mutant individuals, the species offers opportunities for targeted gene expression and [...] Read more.

Drosophila melanogaster (D. melanogaster) has been widely used in biology, including classical genetics, for almost a century. With the entire D. melanogaster genome sequenced and the existence of transgenic and mutant individuals, the species offers opportunities for targeted gene expression and manipulation. Genes involved in the regulation of the animal’s cardiac development include genes associated with the ancient regulatory networks that direct the formation of the cardiac form. However, additional loci can also affect cardiac development, including genes associated with cellular metabolism and protein homeostasis; signaling pathways necessary for the establishment of body segmentation and polarity; homeotic genes involved in the establishment of the animal body plan; and finally, genes encoding chromatin modification enzymes. Conservation in the genetic networks governing cardiac development between D. melanogaster and mammalian vertebrates, coupled with the absence of genetic redundancy in D. melanogaster, allows for the study and evaluation of mutations that could potentially disrupt cardiac development in the former. In this manner, phenotypes in D. melanogaster can be compared with phenotypes present in vertebrate animal models and human patients; this, in turn, allows for comparisons of gene function to be made across different species and for identification of candidate genes with a potential effect on cardiac development. These genes can then be further tested in vertebrate models with possible clinical implications. It is thus the purpose of this comprehensive literature review to summarize and categorize studies evaluating the results of genetic mutations on D. melanogaster cardiac development, as well as uncover any associations between D. melanogaster and similar phenotypes in vertebrates and humans due to effects on the corresponding gene orthologs. Full article

(This article belongs to the Section Molecular and Translational Medicine)

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13 pages, 944 KB

Open AccessArticle

CytoSorb^® Hemadsorption During Microaxial Flow Pump (mAFP) Support in Cardiogenic Shock: A Propensity Score-Matched Cohort Study

by Julian Kreutz, Klevis Mihali, Lukas Harbaum, Georgios Chatzis, Nikolaos Patsalis, Styliani Syntila, Bernhard Schieffer and Birgit Markus

Biomedicines 2025, 13(10), 2568; https://doi.org/10.3390/biomedicines13102568 - 21 Oct 2025

Viewed by 538

Abstract

Background: Despite advances in temporary mechanical circulatory support (tMCS), patients with cardiogenic shock (CS) who are treated with a microaxial flow pump (mAFP; Impella^®, Abiomed) still have a high mortality rate. A dysregulated systemic inflammatory response significantly contributes to multiorgan failure [...] Read more.

Background: Despite advances in temporary mechanical circulatory support (tMCS), patients with cardiogenic shock (CS) who are treated with a microaxial flow pump (mAFP; Impella^®, Abiomed) still have a high mortality rate. A dysregulated systemic inflammatory response significantly contributes to multiorgan failure in this population. CytoSorb^® hemadsorption has emerged as a potential adjunctive therapy for modulating inflammation, but data on its use in CS are limited. Methods: This retrospective, single-center study used propensity score matching analysis (1:1 matching; n = 15 per group) to compare the outcomes of patients receiving mAFP support with and without concomitant CytoSorb therapy. Baseline data (T0), including comorbidities and clinical status at ICU admission, were collected for all patients. In the CytoSorb group, data were collected at two additional time points: 24 h before the start of CytoSorb therapy (T1), and 24 h after its completion (T2). At these time points, laboratory values and parameters on respiratory, hemodynamic, and organ function were assessed. Corresponding data were also collected for matched patients in the non-CytoSorb group at equivalent time points relative to their matched counterparts. Results: In the propensity score-matched cohort, patients treated with CytoSorb exhibited significant improvements between T1 and T2. Specifically, reductions were observed in the vasoactive-inotropic score (p = 0.035), procalcitonin levels (p = 0.041), peak inspiratory pressure (p = 0.036), and positive end-expiratory pressure (p = 0.016). Flow rates through the mAFP declined significantly (p = 0.014), suggesting stabilization of hemodynamics. These changes were not observed in the non-CytoSorb group, where most parameters remained unchanged or exhibited less pronounced trends. We observed a lower in-hospital mortality rate in the CytoSorb group (33.3% versus 46.7%), though the difference was not significant, potentially due to limited statistical power. Conclusions: CytoSorb hemadsorption in mAFP-supported CS was associated with improved hemodynamic stability and reduced inflammatory burden. These findings suggest a potential therapeutic benefit of adjunctive hemadsorption in this high-risk population. Full article

(This article belongs to the Section Molecular and Translational Medicine)

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20 pages, 2139 KB

Open AccessSystematic Review

Does Phototherapy Affect Ductus Arteriosus Closure in Preterm Infants ≤32 Weeks of Gestation, and Can We Influence This Through Chest Shielding? Review of the Literature and a Meta-Analysis

by Marta Simon, Zsuzsanna Gall, Monika Rusneac, Amalia Fagarasan, Raluca Marian, Madalina Anciuc-Crauciuc, Andreea Racean, Andrea Noemi Toth and Manuela Cucerea

Biomedicines 2025, 13(10), 2567; https://doi.org/10.3390/biomedicines13102567 - 21 Oct 2025

Viewed by 440

Abstract

Background: Persistency of patent ductus arteriosus is the main cardiac condition in the preterm population born before 32 completed weeks of gestation with possible short- and long-term hemodynamic disturbances leading to vast morbidity. Jaundice is present in the majority of very preterms [...] Read more.

Background: Persistency of patent ductus arteriosus is the main cardiac condition in the preterm population born before 32 completed weeks of gestation with possible short- and long-term hemodynamic disturbances leading to vast morbidity. Jaundice is present in the majority of very preterms needing phototherapy, that also may have an influence on immature hemodynamics. The objectives of this review and meta-analysis were to find relevant evidence of whether chest shielding during phototherapy does or does not have an impact on the ductus arteriosus patency and hemodynamics. Methods: we reviewed the literature and performed a meta-analysis of five randomized controlled trials regarding chest shielding effect on the ductus arteriosus closure. Results: A total of 452 infants, with a mean gestational age of 28.04 weeks and mean birth weight of 1004.8 g were included in our meta-analysis, where we found an RR of 0.6 for developing PDA during phototherapy and chest shielding (95% CI: 0.37; 0.96. prediction interval: 0.18; 1.99) while development of hemodynamically significant PDA had RR = 0.57, within 95% CI: 0.3; 1.06, and a predictive interval between: 0.11; 2.93. Conclusions: Although the estimated RR may suggest a possible moderate protective role of the chest shield regarding development of PDA during phototherapy, the wideness of the predictive intervals, that include no effect, as well as the small number of eligible trials with heterogeneity between them, make the available data insufficient to evaluate the effectiveness of chest shielding during phototherapy. For more conclusive evidence there is a need for well-designed, blinded, multicenter randomized controlled trials with standardized assessment addressing to a more compact target population, knowing the large physiological differences among preterm infants of different gestational ages. Full article

(This article belongs to the Special Issue Maternal-Fetal and Neonatal Medicine)

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Graphical abstract

24 pages, 2791 KB

Open AccessArticle

Clinical and Therapeutic Insights into Sepsis: A Retrospective Observational Study of Inflammatory Markers, and Outcomes

by Dragoș Ștefan Lazăr, Adina-Alexandra Nanu, Ilie-Andrei Condurache, Casandra Bulescu, Catrinel Tudosie, Alexandra Ioana Grigore, Corneliu Petru Popescu and Simin Aysel Florescu

Biomedicines 2025, 13(10), 2566; https://doi.org/10.3390/biomedicines13102566 - 21 Oct 2025

Viewed by 574

Abstract

Introduction: Sepsis is a life-threatening condition caused by dysregulated host responses to infection, leading to organ failure and high mortality. Early recognition, especially in vulnerable populations, remains challenging due to variable presentations. Key biomarkers like CRP, procalcitonin, fibrinogen, and neutrophil-to-lymphocyte ratio (NLR) aid [...] Read more.

Introduction: Sepsis is a life-threatening condition caused by dysregulated host responses to infection, leading to organ failure and high mortality. Early recognition, especially in vulnerable populations, remains challenging due to variable presentations. Key biomarkers like CRP, procalcitonin, fibrinogen, and neutrophil-to-lymphocyte ratio (NLR) aid in diagnosis, monitoring, and prognosis. Rapid identification and targeted therapy are critical, particularly amid rising antimicrobial resistance. This study aims to analyze the relationship between early biomarker levels and patient outcomes, focusing on mortality risk prediction within the first week of hospitalization. Methods: A retrospective study of 198 sepsis patients hospitalized in Bucharest, Romania, between January and December 2024, analyzing inflammatory biomarkers at admission—T0, 48–72 h—T1, and one week—T2, to identify predictors of clinical outcomes. Results: In patients under 65 years old, fibrinogen, CRP, and NLR significantly decreased from T0 to T2, especially in survivors. In contrast, patients over 65 years old showed less consistent biomarker changes, with higher mortality associated, with comorbidities such as heart failure and cancer. Overall, early reductions in inflammatory markers correlated with better outcomes, highlighting their prognostic value in sepsis management. Conclusions: In sepsis patients over 65 years old, a stable or rising neutrophil-to-lymphocyte ratio (NLR) and fibrinogen levels after the first week of hospitalization may indicate a poor prognosis, whereas decreasing levels suggest a better chance of survival. Full article

(This article belongs to the Section Microbiology in Human Health and Disease)

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16 pages, 15044 KB

Open AccessArticle

Effects of Methylcobalamin on Mitochondrial Alterations in Schwann Cells Under Oxidative Stress

by Qicheng Li, Shiyan Liu, Lu Zhang, Tianze Sun and Yuhui Kou

Biomedicines 2025, 13(10), 2565; https://doi.org/10.3390/biomedicines13102565 - 21 Oct 2025

Viewed by 454

Abstract

Background/Objectives: Peripheral neuropathy (PN) triggers early oxidative stress, disrupting Schwann cell homeostasis. In this context, mitochondria serve as a primary source and vulnerable target of reactive oxygen species (ROS). Here, we investigated whether methylcobalamin (MeCbl) mitigates oxidative stress-induced mitochondrial dysfunction. Methods: [...] Read more.

Background/Objectives: Peripheral neuropathy (PN) triggers early oxidative stress, disrupting Schwann cell homeostasis. In this context, mitochondria serve as a primary source and vulnerable target of reactive oxygen species (ROS). Here, we investigated whether methylcobalamin (MeCbl) mitigates oxidative stress-induced mitochondrial dysfunction. Methods: RSC96 cells were exposed to H₂O₂ to model oxidative injury, then treated with MeCbl. Mitochondrial network integrity was evaluated using super-resolution imaging coupled with quantitative morphometric analysis. RNA-sequencing was performed to identify differentially expressed genes (DEGs) and enriched biological pathways. Additionally, a network-pharmacology approach was employed to intersect the predicted MeCbl targets with the transcriptomic signature. Results: MeCbl treatment alleviated H₂O₂-induced mitochondrial fragmentation, restoring the interconnected reticulum characterized by increased branch number, total area, and a reduction in punctate mitochondria. Transcriptome analyses revealed the reprogramming of stress-response pathways. The DEGs were significantly enriched in processes including mitochondrial organization and dynamics, redox homeostasis, protein quality control, and pro-survival signaling. Network pharmacology demonstrated convergence between the MeCbl targets and DEGs at core nodes governing mitochondrial quality control and antioxidant defense, thereby providing a mechanistic basis for the imaging phenotypes. Conclusions: MeCbl improved the mitochondrial structure and remodeled the stress-response pathways in Schwann cells under oxidative stress. By linking high-resolution organelle phenotypes to molecular networks, these findings support MeCbl as a rational adjunct to mitigate oxidative stress-driven peripheral neuropathy and identify an intervenable regulatory axis for future targeted therapies. Full article

(This article belongs to the Section Cell Biology and Pathology)

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Graphical abstract

3 pages, 2851 KB

Open AccessCorrection

Correction: Milusheva et al. In Silico, In Vitro, and Ex Vivo Biological Activity of Some Novel Mebeverine Precursors. Biomedicines 2023, 11, 605

by Miglena Milusheva, Vera Gledacheva, Iliyana Stefanova, Mina Pencheva, Rositsa Mihaylova, Yulian Tumbarski, Paraskev Nedialkov, Emiliya Cherneva, Mina Todorova and Stoyanka Nikolova

Biomedicines 2025, 13(10), 2564; https://doi.org/10.3390/biomedicines13102564 - 21 Oct 2025

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Abstract

In the original publication [...] Full article

(This article belongs to the Section Drug Discovery, Development and Delivery)

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22 pages, 847 KB

Open AccessArticle

The Inflammatory Footprint of Anti-Breast Cancer Treatments and Psychosocial Factors in Women Undergoing Chemotherapy

by Magda A. Oliveira, Susana S. Almeida, Gabriela Martins, Inês Godinho, Carlos Palmeira, Maria Emília Sousa, Lia Fernandes, Rui Medeiros and Marina Prista Guerra

Biomedicines 2025, 13(10), 2563; https://doi.org/10.3390/biomedicines13102563 - 21 Oct 2025

Viewed by 515

Abstract

Background/Objectives: Despite the well-recognized role of inflammation in breast cancer course, the biological mechanisms involved in its pathophysiology are complex, heterogeneous, and still unclear. However, evidence shows that cancer treatments and stress system responses impact the patient’s inflammatory status. We aim to [...] Read more.

Background/Objectives: Despite the well-recognized role of inflammation in breast cancer course, the biological mechanisms involved in its pathophysiology are complex, heterogeneous, and still unclear. However, evidence shows that cancer treatments and stress system responses impact the patient’s inflammatory status. We aim to analyze the inflammatory footprint of anti-breast cancer treatments and psychosocial factors by observing the evolution of inflammatory and psychosocial markers pre- and post-chemotherapy; to examine the associations between pro- and anti-inflammatory cytokines with psychosocial factors after chemotherapy; and to identify vulnerability/resilience variables that may improve patients’ referral for psycho-oncological interventions before/after chemotherapy. Methods: We performed a well-controlled cohort study of premenopausal women diagnosed with stage I to III breast cancer undergoing chemotherapy. Patients were longitudinally evaluated at pre-chemotherapy (post-surgery in the adjuvant cohort) and post-chemotherapy. Both evaluations included clinical, immunological, and psychosocial data. Results: A significant decrease in TNF-α (p = 0.001) was observed in the adjuvant cohort compared to the neoadjuvant cohort. After chemotherapy, we found a significant decline in IL-17a, TNF-α, and IL-10 (p = 0.000, 0.000, 0.020), reinforcing the influence of chemotherapy on immunocompetence. Significant relations (p < 0.01) were found between the inflammatory biomarkers that decreased post-chemotherapy and psychosocial factors. Venting and instrumental/emotional support coping played the greatest role in immunological–psychological interactions. Conclusions: The findings confirm an inflammatory footprint, linking the complex interplay between breast tumors, anti-breast cancer treatments, and psychosocial factors. By supporting the immunoregulatory role of biological and psychosocial factors in immunocompetence, our findings bring potential insights into a biopsychosocial approach that targets both survival and psychological adjustment outcomes. Full article

(This article belongs to the Special Issue Women’s Special Issue Series: Biomedicines (2nd Edition))

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17 pages, 6213 KB

Open AccessArticle

Preoperative Prediction of Axillary Lymph Node Metastasis in Breast Cancer Using Radiomics Features of Voxel-Wise DCE-MRI Time-Intensity-Curve Profile Maps

by Ya Ren, Kexin Chen, Meng Wang, Jie Wen, Sha Feng, Honghong Luo, Cuiju He, Yuan Guo, Dehong Luo, Xin Liu, Dong Liang, Hairong Zheng, Na Zhang and Zhou Liu

Biomedicines 2025, 13(10), 2562; https://doi.org/10.3390/biomedicines13102562 - 21 Oct 2025

Viewed by 593

Abstract

Objective: Axillary lymph node (ALN) status in breast cancer is pivotal for guiding treatment and determining prognosis. The study aimed to explore the feasibility and efficacy of a radiomics model using voxel-wise dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) time-intensity-curve (TIC) profile maps [...] Read more.

Objective: Axillary lymph node (ALN) status in breast cancer is pivotal for guiding treatment and determining prognosis. The study aimed to explore the feasibility and efficacy of a radiomics model using voxel-wise dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) time-intensity-curve (TIC) profile maps to predict ALN metastasis in breast cancer. Methods: A total of 615 breast cancer patients who underwent preoperative DCE-MRI from October 2018 to February 2024 were retrospectively enrolled and randomly allocated into training (n = 430) and testing (n = 185) sets (7:3 ratio). Based on wash-in rate, wash-out enhancement, and wash-out stability, each voxel within manually segmented 3D lesions that were categorized into 1 of 19 TIC subtypes from the DCE-MRI images. Three feature sets were derived: composition ratio (type-19), radiomics features of TIC subtypes (type-19-radiomics), and radiomics features of third-phase DCE-MRI (phase-3-radiomics). Student’s t-test and the least absolute shrinkage and selection operator (LASSO) was used to select features. Four models (type-19, type-19-radiomics, type-19-combined, and phase-3-radiomics) were constructed by a support vector machine (SVM) to predict ALN status. Model performance was assessed using sensitivity, specificity, accuracy, F1 score, and area under the curve (AUC). Results: The type-19-combined model significantly outperformed the phase-3-radiomics model (AUC = 0.779 vs. 0.698, p < 0.001; 0.674 vs. 0.559) and the type-19 model (AUC = 0.779 vs. 0.541, p < 0.001; 0.674 vs. 0.435, p < 0.001) in cross-validation and independent testing sets. The type-19-radiomics showed significantly better performance than the phase-3-radiomics model (AUC = 0.764 vs. 0.698, p = 0.002; 0.657 vs. 0.559, p = 0.037) and type-19 model (AUC = 0. 764 vs. 0.541, p < 0.001; 0.657 vs. 0.435, p < 0.001) in cross-validation and independent testing sets. Among four models, the type-19-combined model achieved the highest AUC (0.779, 0.674) in cross-validation and testing sets. Conclusions: Radiomics analysis of voxel-wise DCE-MRI TIC profile maps, simultaneously quantifying temporal and spatial hemodynamic heterogeneity, provides an effective, noninvasive method for predicting ALN metastasis in breast cancer. Full article

(This article belongs to the Special Issue Breast Cancer Research: Charting Future Directions)

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14 pages, 1316 KB

Open AccessArticle

Branched-Chain Amino Acid Intake and Risk of Incident Type 2 Diabetes: Results from the SUN Cohort

by Víctor de la O, Telmo Bretos-Azcona, Francisco Javier Basterra-Gortari, Carmen de la Fuente-Arrillaga, Miguel Ruiz-Canela, Miguel Ángel Martínez-González and Maira Bes-Rastrollo

Biomedicines 2025, 13(10), 2561; https://doi.org/10.3390/biomedicines13102561 - 21 Oct 2025

Viewed by 655

Abstract

Background/Objectives: While many studies have explored the association between circulating branched-chain amino acids (BCAAs) and type 2 diabetes mellitus (T2DM), evidence on the prospective relationship between dietary BCAA intake and T2DM risk remains limited. We aimed to explore this relationship—both total and [...] Read more.

Background/Objectives: While many studies have explored the association between circulating branched-chain amino acids (BCAAs) and type 2 diabetes mellitus (T2DM), evidence on the prospective relationship between dietary BCAA intake and T2DM risk remains limited. We aimed to explore this relationship—both total and by dietary source—in a Mediterranean cohort. Methods: We used data from the SUN Project, a prospective and dynamic cohort of Spanish university graduates initiated in 1999. Dietary intake was assessed with a validated 136-item food frequency questionnaire at baseline and at 10 years. BCAA intake (valine, leucine, isoleucine) was estimated using the USDA amino acid database and adjusted for energy intake by the residual method. Participants were followed biennially through questionnaires to identify incident T2DM cases, confirmed by a supplementary questionnaire and medical report, following the ADA diagnostic criteria. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs), adjusting for potential confounders across four multivariable models. BCAA intake was modeled both categorically (tertiles) and continuously (per 0.5% energy or 5 g/day increase). Analyses were stratified by age and recruitment period. Results: After exclusions, 20,154 participants were included (mean follow-up: 14.67 ± 5.8 years), with 220 incident T2DM cases identified. For each 0.5% energy increment intake from BCAA, there was no association with T2DM (adjusted HR: 1.01; 95% CI: 0.69–1.20). Among men, the adjusted HR was 0.91, 95% CI: 0.69–1.20. Among women, it was 1.40, 95% CI: 0.94–2.09. In the overall cohort, higher BCAA intake showed a non-significant inverse association with the T2DM risk when comparing extreme tertiles (HR = 0.81; 95% CI: 0.48–1.37), which strengthened when repeated dietary measures were considered (HR = 0.70; 95% CI: 0.46–1.06, p-trend = 0.06). Analyses by BCAA sources (animal vs. plant) and stratified by sex, weight status, and age did not reveal consistent patterns, though exploratory findings suggested potential effect modification by sex and adiposity. Sensitivity analyses confirmed the lack of robust associations, with some subgroup-specific signals being limited by low event numbers and wide CIs. Conclusions: Given the power limitations and the modest, non-significant associations observed, these findings should be considered preliminary evidence that may help guide future research on the role of dietary BCAAs in glucose metabolism and diabetes risk. Full article

(This article belongs to the Special Issue Diabetes: Comorbidities, Therapeutics and Insights (3rd Edition))

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11 pages, 2723 KB

Open AccessArticle

A Fluorescence-Based Histidine-Imidazole Polyacrylamide Gel Electrophoresis (HI-PAGE) Method for Rapid and Practical Lipoprotein Profiling and LDL-C Quantification in Clinical Samples

by Yasuhiro Takenaka, Ikuo Inoue, Masaaki Ikeda and Yoshihiko Kakinuma

Biomedicines 2025, 13(10), 2560; https://doi.org/10.3390/biomedicines13102560 - 21 Oct 2025

Viewed by 370

Abstract

Background: Polyacrylamide gel electrophoresis (PAGE) has long been used for lipoprotein analysis, enabling the separation and profiling of lipoprotein fractions such as LDL and HDL. However, conventional disc PAGE systems are limited by low throughput and inability to directly compare multiple samples [...] Read more.

Background: Polyacrylamide gel electrophoresis (PAGE) has long been used for lipoprotein analysis, enabling the separation and profiling of lipoprotein fractions such as LDL and HDL. However, conventional disc PAGE systems are limited by low throughput and inability to directly compare multiple samples under identical conditions. Alternative methods, including high-performance liquid chromatography and agarose gel electrophoresis, require specialized equipment and expertise, limiting their clinical utility. Methods: We present a colorimetric and fluorescence-based histidine-imidazole PAGE (HI-PAGE) system that provides rapid, cost-effective, and reproducible separation and profiling of lipoproteins in human serum. By combining electrophoretic separation with lipid-specific fluorescent staining using Nile Red, the fluorescence-based HI-PAGE (fHI-PAGE) not only visualizes distinct migration patterns of lipoprotein fractions, but also enables the quantification of LDL-cholesterol (LDL-C). Clear resolution of LDL and other lipoprotein fractions was achieved within 1 h without band distortion, allowing for direct comparison of multiple samples on a single gel. Results: We validated fHI-PAGE using serum from healthy individuals and patients, demonstrating that its fluorescence-based detection was more sensitive than conventional Sudan Black B staining while providing LDL-C estimates concordant with values calculated by the Friedewald formula. Moreover, fHI-PAGE proved advantageous in cases of hypertriglyceridemia, where Friedewald calculations are unreliable. Conclusions: These findings establish fHI-PAGE as a practical and clinically applicable platform for simultaneous lipoprotein profiling and LDL-C quantification. Full article

(This article belongs to the Section Biomedical Engineering and Materials)

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15 pages, 2606 KB

Open AccessArticle

Specific microRNAs for Heart Failure: Reference Values in Whole Blood

by Radka Sigutova, Lukas Evin, Pavlina Kusnierova, David Stejskal, Frantisek Vsiansky, Eva Bace, Eliska Kufova, Gabriela Kubikova, Zdenek Svagera, Marian Branny and Jan Vaclavik

Biomedicines 2025, 13(10), 2559; https://doi.org/10.3390/biomedicines13102559 - 20 Oct 2025

Viewed by 984

Abstract

Background: The objective of this study was to validate reference values for eight selected microRNAs (miRNAs) in a population of healthy individuals. The selected miRNAs (hsa-miR-21-5p, hsa-miR-23a-3p, hsa-miR-142-5p and hsa-miR-126-3p, hsa-miR-499a-5p, hsa-miR-195-5p, hsa-miR-1-3p, hsa-miR-29a-3p) have an important role in heart failure. Methods: Ninety-nine [...] Read more.

Background: The objective of this study was to validate reference values for eight selected microRNAs (miRNAs) in a population of healthy individuals. The selected miRNAs (hsa-miR-21-5p, hsa-miR-23a-3p, hsa-miR-142-5p and hsa-miR-126-3p, hsa-miR-499a-5p, hsa-miR-195-5p, hsa-miR-1-3p, hsa-miR-29a-3p) have an important role in heart failure. Methods: Ninety-nine individuals were selected for this study. Specific microRNAs were isolated from whole blood and quantified using the microRNA enzymatic immunoassay (miREIA) method. Reference intervals were evaluated with respect to age and sex. Statistical analyses were performed using MedCalc (v22.021) and R software, Version 4.1.2. Results: Reference values (2.5th and 97.5th percentile values and their 90% confidence intervals) were determined for hsa-miR-21-5p: 1.45 to 96.3 pmol/L, hsa-miR-23a-3p: 13.0 to 432 pmol/L, hsa-miR-126-3p: 5.67 to 66.5 pmol/L, hsa-miR-142-5p: 37.4 to 293 pmol/L, hsa-miR-195-5p: 11.5 to 254 pmol/L, hsa-miR-1-3p: 50.6 to 1800 pmol/L, hsa-miR-499a-5p: 8.90 to 82.5 pmol/L and hsa-miR-29a-3p: 22.9 to 210 pmol/L. The median age of the included individuals was 44 years (range: 23–75 years). No sex-related differences were observed in the reference intervals of the microRNAs (p < 0.05). Except for hsa-miR-21-5p (RS = −0.208; p = 0.043), no significant age-related associations were found for the other microRNAs (p < 0.05). However, due to the limited number of individuals in the stratified subgroups, reference intervals were not calculated for these subgroups. Conclusions: In this study, reference intervals for eight specific miRNAs associated with heart failure were determined. The results are unique for assessment in further clinical research, given that reference intervals in absolute values have not yet been published. Full article

(This article belongs to the Special Issue MicroRNAs in Precision Medicine: Regulation, Biomarkers and Novel Therapeutics)

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37 pages, 7917 KB

Open AccessReview

Photothermal Combination Therapy for Metastatic Breast Cancer: A New Strategy and Future Perspectives

by Zun Wang, Ikram Hasan, Yinghe Zhang, Tingting Peng and Bing Guo

Biomedicines 2025, 13(10), 2558; https://doi.org/10.3390/biomedicines13102558 - 20 Oct 2025

Viewed by 1886

Abstract

Metastatic breast cancer (MBC) remains one of the most aggressive and fatal malignancies in women, primarily due to tumor heterogeneity, multidrug resistance, and the limitations of conventional therapeutic approaches. Aim: This review aims to evaluate recent advances in nanomaterial-based photothermal therapy (PTT) platforms [...] Read more.

Metastatic breast cancer (MBC) remains one of the most aggressive and fatal malignancies in women, primarily due to tumor heterogeneity, multidrug resistance, and the limitations of conventional therapeutic approaches. Aim: This review aims to evaluate recent advances in nanomaterial-based photothermal therapy (PTT) platforms and their potential in the treatment of metastatic breast cancer. Method: A comprehensive analysis of current literature was conducted to examine how various nanomaterials are engineered for targeted PTT, with particular emphasis on their mechanisms of action, synergistic applications with chemotherapy, immunotherapy, and photodynamic therapy, as well as their capacity to overcome challenges associated with targeting metastatic niches. Results: The findings indicate that nanotechnology-enabled PTT provides spatiotemporal precision, efficient tumor ablation, and reduced systemic toxicity, while significantly enhancing therapeutic outcomes when integrated into multimodal treatment strategies. Recent preclinical studies and early clinical trials further underscore advancements in imaging guidance, thermal efficiency, and site-specific drug delivery; however, issues related to biocompatibility, safety, and large-scale clinical translation remain unresolved. Conclusions: Nanomaterial-assisted PTT holds substantial promise for improving therapeutic efficacy against metastatic breast cancer. Future research should prioritize optimizing imaging resolution, minimizing adverse effects, and addressing translational challenges to accelerate clinical integration and ultimately enhance health outcomes for women. Full article

(This article belongs to the Section Cancer Biology and Oncology)

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14 pages, 2296 KB

Open AccessArticle

Deep-Learning Model for Iris and Eyebrow Segmentation and Automation of Eye Landmark Measurements in Acquired Ptosis

by Dain Yoo and Hyun Jin Shin

Biomedicines 2025, 13(10), 2557; https://doi.org/10.3390/biomedicines13102557 - 20 Oct 2025

Viewed by 1581

Abstract

Background: Acquired ptosis is a common eyelid disorder in elderly patients, causing visual disturbance and cosmetic concerns. Accurate evaluation of periocular anatomy, including eyebrow and iris position, is essential for surgical planning, but current manual assessments are time-consuming and subjective. Objectives: [...] Read more.

Background: Acquired ptosis is a common eyelid disorder in elderly patients, causing visual disturbance and cosmetic concerns. Accurate evaluation of periocular anatomy, including eyebrow and iris position, is essential for surgical planning, but current manual assessments are time-consuming and subjective. Objectives: This study aimed to develop deep-learning models for iris and eyebrow segmentation to automate eye landmark measurements and enable objective, standardized analysis in patients with acquired ptosis. Methods: We retrospectively collected 612 facial images from 209 ptosis patients. Images were labeled for iris and eyebrow segmentation and split into training, validation, and test sets (8:1:1). A deep-learning model was developed to automatically segment the iris and eyebrow regions and automatically measure seven landmarks: MRD1, MRD2, medial eyebrow end, medial limbus, pupil center, lateral limbus, and lateral eyebrow end. Results: The iris segmentation model achieved accuracy of 99.7%, precision of 97.6%, recall of 98.3%, an F1 score of 97.9%, and intersection over union of 95.9%. The corresponding metrics for the eyebrow segmentation model were 98.6%, 92.6%, 91.5%, 91.5%, and 85.0%. The mean absolute percentage error and root mean square error for the automated landmark measurements were 4.00% and 2.48 mm, respectively. Conclusions: The high performance of the segmentation models and the automated measurements supports their potential use for objective and standardized analyses of acquired ptosis. These findings may aid the future development of predictive tools for use in surgical planning. Full article

(This article belongs to the Section Molecular and Translational Medicine)

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12 pages, 527 KB

Open AccessArticle

Diagnostic Accuracy of the Cobas^® MTB and Cobas MTB/RIF-INH Assays on Sputum and the Cobas MTB Assay on Tongue Swabs for Mycobacterium tuberculosis Complex Detection in Symptomatic Adults in South Africa

by Anura David, Lyndel Singh, Manuel Pedro da Silva, Keneilwe Peloakgosi-Shikwambani, Zanele Nsingwane, Violet Molepo, Wendy Stevens and Lesley Erica Scott

Biomedicines 2025, 13(10), 2556; https://doi.org/10.3390/biomedicines13102556 - 20 Oct 2025

Viewed by 1283

Abstract

Background/Objectives: Accurate and rapid detection of Mycobacterium tuberculosis complex (MTBC) and drug resistance is essential for effective tuberculosis (TB) management, particularly in high-burden settings. The Cobas^® MTB and Cobas MTB/RIF-INH assays are moderate-complexity nucleic acid amplification tests that detect MTBC and [...] Read more.

Background/Objectives: Accurate and rapid detection of Mycobacterium tuberculosis complex (MTBC) and drug resistance is essential for effective tuberculosis (TB) management, particularly in high-burden settings. The Cobas^® MTB and Cobas MTB/RIF-INH assays are moderate-complexity nucleic acid amplification tests that detect MTBC and resistance to rifampicin (RIF) and isoniazid (INH). Methods: This study evaluated the clinical diagnostic performance of the Cobas assays on sputum, using liquid culture as the reference standard and Xpert MTB/RIF Ultra (Xpert Ultra) for comparison. Diagnostic accuracy of the Cobas MTB assay on tongue swabs (TS) was also assessed. Results: In a study population (n = 354) with 56% HIV prevalence, the overall sensitivity and specificity of Cobas MTB on sputum was 93.8% (95% CI: 84.8–98.3) and 100% (95% CI: 98.7–100) compared with culture. The assay showed almost perfect agreement with Xpert Ultra (Cohen’s kappa = 0.904). Among HIV-positive participants, sensitivity was 88.2% (95% CI: 72.5–96.7). RIF resistance profiling by Cobas MTB/RIF-INH was fully concordant with culture and Xpert Ultra. Three INH-resistant cases were missed, likely due to genotypic–phenotypic discordance. Although specimen numbers were small, TS demonstrated better diagnostic accuracy when using a diluted (66%) microbial inactivation solution. Conclusions: The Cobas MTB and MTB/RIF-INH assays demonstrated high diagnostic accuracy compared to culture and Xpert Ultra on sputum. Findings support TS as an alternative specimen type for MTBC detection using an optimized protocol. These findings underscore the potential of the Cobas assays as reliable alternatives for TB and resistance diagnostics, particularly in settings where rapid, accurate detection of MTBC and RIF or INH resistance is crucial. Full article

(This article belongs to the Special Issue Molecular Diagnostics and Monitoring in Tuberculosis)

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44 pages, 1792 KB

Open AccessReview

Plagued by the Past, Pressed by the Present: A One Health Perspective on Yersinia pestis

by Andrea Ciammaruconi, Maria Di Spirito, Chiara Pascolini, Filippo Molinari, Orr Rozov, Marzia Cavalli, Giulia Campoli, Nathalie Totaro, Elisa Recchia, Silvia Chimienti, Anella Monte, Ferdinando Spagnolo, Florigio Lista, Raffaele D’Amelio and Silvia Fillo

Biomedicines 2025, 13(10), 2555; https://doi.org/10.3390/biomedicines13102555 - 20 Oct 2025

Viewed by 2189

Abstract

Yersinia pestis, the causative agent of plague, is arguably the most devastating pathogen in human history. Paleogenomic studies indicate its presence as early as the Neolithic era. It evolved from Yersinia pseudotuberculosis, with divergence estimates ranging from 1500 to 20,000 years [...] Read more.

Yersinia pestis, the causative agent of plague, is arguably the most devastating pathogen in human history. Paleogenomic studies indicate its presence as early as the Neolithic era. It evolved from Yersinia pseudotuberculosis, with divergence estimates ranging from 1500 to 20,000 years ago, most often placed around 5000 years ago. Its natural reservoirs are wild mammals, particularly rodents, with fleas serving as vectors, while humans are incidental hosts. Over time, Y. pestis has acquired multiple virulence factors that disrupt immune responses and can lead to rapid, often fatal disease. Because the bacterium is maintained in wildlife cycles and can spill over to domestic animals, eradication is difficult, if not impossible. Nevertheless, mitigation is achievable using a One Health approach integrating human health, animal health, and the health of the environment. Neither vaccines nor monoclonal antibodies are currently licensed in most Western countries, thus, antibiotics remain the mainstay of therapy. Timely administration, ideally within 24 h of symptom onset, is critical, particularly in pneumonic forms. Phage therapy is under investigation as a potential treatment. Though often neglected in high-income settings, plague remains endemic in several regions, with the highest burden reported in Madagascar and the Democratic Republic of the Congo. Full article

(This article belongs to the Section Microbiology in Human Health and Disease)

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12 pages, 3574 KB

Open AccessArticle

Spatial Proximity of Cancer-Associated Fibroblasts to Tumor and Osteoclasts Suggests a Coordinating Role in OSCC-Induced Bone Invasion: A Preliminary Study

by Nobuyuki Sasahara, Masayuki Kaneko, Takumi Kitaoka, Michihisa Kohno, Takanobu Kabasawa, Naing Ye Aung, Rintaro Ohe, Mitsuyoshi Iino and Mitsuru Futakuchi

Biomedicines 2025, 13(10), 2554; https://doi.org/10.3390/biomedicines13102554 - 20 Oct 2025

Viewed by 496

Abstract

Background: Jawbone invasion is a common and prognostically unfavorable feature of oral squamous cell carcinoma (OSCC). Although cancer-associated fibroblasts (CAFs) are recognized for their role in tumor progression, their spatial dynamics at the tumor–bone interface remain poorly understood. Methods: We analyzed [...] Read more.

Background: Jawbone invasion is a common and prognostically unfavorable feature of oral squamous cell carcinoma (OSCC). Although cancer-associated fibroblasts (CAFs) are recognized for their role in tumor progression, their spatial dynamics at the tumor–bone interface remain poorly understood. Methods: We analyzed 14 OSCC specimens with confirmed jawbone invasion using histopathological and immunohistochemical techniques. Digital pathology combined with AI-assisted image analysis was employed to quantify and visualize the spatial distribution of OSCC cells (RANKL-positive), CAFs (α-SMA and FAP-positive), and osteoclasts (cathepsin K-positive) within defined regions of interest at the tumor–bone invasive front. Results: A consistent laminar stromal region enriched in CAFs was observed between the tumor nests and jawbone. CAFs were spatially clustered near OSCC cells and osteoclasts, with 81% and 74% residing within 50 μm, respectively. On average, 11.4 CAFs were present per OSCC cell and 23.2 per osteoclast. These spatial proximities were largely preserved irrespective of stromal thickness, suggesting active bidirectional cellular interactions. Conclusions: Our findings demonstrate that CAFs are strategically positioned to facilitate intercellular signaling between tumor cells and osteoclasts, potentially coordinating OSCC proliferation and bone resorption. This study highlights the utility of AI-assisted spatial histology in unraveling tumor microenvironmental dynamics and proposes CAFs as potential therapeutic targets in OSCC-induced osteolytic invasion. Full article

(This article belongs to the Section Molecular and Translational Medicine)

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15 pages, 598 KB

Open AccessArticle

Association of Intracranial Plaque Features with the Severity of White Matter Hyperintensities in Middle-Aged and Older Community-Dwelling Adults

by Yangyang Cheng, Lihua Lai, Jieqi Luo and Michael Tin Cheung Ying

Biomedicines 2025, 13(10), 2553; https://doi.org/10.3390/biomedicines13102553 - 20 Oct 2025

Viewed by 524

Abstract

Background/Objectives: Despite the reported correlation between white matter hyperintensity (WMH) and intracranial atherosclerosis (ICAS), little is known about the association between intracranial plaque imaging characteristics and the severity of WMH. This study aimed to investigate the relationship between plaque imaging features in [...] Read more.

Background/Objectives: Despite the reported correlation between white matter hyperintensity (WMH) and intracranial atherosclerosis (ICAS), little is known about the association between intracranial plaque imaging characteristics and the severity of WMH. This study aimed to investigate the relationship between plaque imaging features in the major intracranial large arteries and the severity of WMH by high-resolution magnetic resonance imaging (HR-MRI) in a local community-based cohort. Methods: Stroke-free Chinese aged over 45 years old were recruited. Plaque imaging features of intracranial arteries identified in middle cerebral arteries (MCAs), vertebral arteries (VAs), and basilar arteries (BAs) were analyzed. The plaque characteristics were compared between subjects with or without moderate-to-severe WMH (Fazekas score > 2), and their independent association with the severity of WMH was also assessed using multivariate logistic regression analysis. Results: In the cohort of 272 subjects (mean age, 63.4 ± 6.8 years old; males, n = 118), 24.6% with moderate-to-severe WMH had a significantly higher prevalence of ICAS, eccentric lesions, diffuse thickening pattern, and a heavier plaque burden in the intracranial major arteries compared to those without moderate-to-severe WMH. After adjusting for confounding factors, multivariate logistic regression analysis showed that an eccentric pattern of plaque lesion was independently associated with moderate-to-severe WMH. Conclusions: Eccentric lesions in the major intracranial large arteries, but not diffuse thickening patterns, luminal stenosis, and plaque burden, were independently associated with a greater burden of WMHs among middle-aged or older adults. Eccentricity of major intracranial large artery lesions may be a potential imaging marker to assess WMH burden. Understanding the correlation between atherosclerotic patterns and the severity of WMH would aid in early stratifying the future clinical risk of cerebrovascular events and support the development of individualized treatment strategies. Further studies are warranted to investigate its value in predicting future cerebrovascular events. Full article

(This article belongs to the Section Neurobiology and Clinical Neuroscience)

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20 pages, 1133 KB

Open AccessReview

Molecular Mechanisms of Thyroid Hormone Signaling in Thyroid Cancer: Oncogenesis, Progression, and Therapeutic Implications

by Changhao Zhou, Wei Liu, Jiaojiao Zheng, Qiao Wu and Zhilong Ai

Biomedicines 2025, 13(10), 2552; https://doi.org/10.3390/biomedicines13102552 - 20 Oct 2025

Viewed by 1162

Abstract

Thyroid cancer, as a highly hormone-dependent malignancy, is significantly regulated by thyroid hormones (T3/T4) and thyroid-stimulating hormone (TSH) signaling in its initiation and progression. This article comprehensively reviews the roles of thyroid hormones and their regulatory factor TSH in thyroid carcinogenesis and development, [...] Read more.

Thyroid cancer, as a highly hormone-dependent malignancy, is significantly regulated by thyroid hormones (T3/T4) and thyroid-stimulating hormone (TSH) signaling in its initiation and progression. This article comprehensively reviews the roles of thyroid hormones and their regulatory factor TSH in thyroid carcinogenesis and development, addressing related research from molecular mechanisms and clinical correlations to therapeutic strategies. It focuses on elucidating the impact of key mechanisms—such as elevated integrin αvβ3 expression and TRβ receptor mutations under hyperthyroid or hypothyroid conditions—on tumor progression. Furthermore, it evaluates the clinical utility and potential risks of TSH suppression therapy in patients stratified by risk, aiming to provide a theoretical basis for optimizing individualized treatment strategies. Full article

(This article belongs to the Section Cancer Biology and Oncology)

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13 pages, 849 KB

Open AccessArticle

The Role of Perinatal Complications in Neurodevelopmental Outcomes of ART-Conceived Children: Prognostic Model for Brain Immaturity

by Sevara Ilmuratova, Vyacheslav Lokshin, Zhanar Nurgaliyeva, Kаnatzhan Kеmelbekov, Gulshat Kulniyazova, Bibigul Abdykalykova, Roza Seisebayeva, Karlygash Zhubanysheva, Gulmira Altynbayeva, Gulnar Mukhambetova, Ainur Sadykova, Damir Marapov, Valeriya Nekhorosheva and Lyazat Manzhuova

Biomedicines 2025, 13(10), 2551; https://doi.org/10.3390/biomedicines13102551 - 20 Oct 2025

Viewed by 928

Abstract

Background/Objectives: Since the first successful birth following assisted reproductive technologies (ART) several decades ago, the global population of ART-conceived children has surpassed 13 million, with over 40,000 born in Kazakhstan. Despite this growth, questions remain about their long-term neurological outcomes, with existing [...] Read more.

Background/Objectives: Since the first successful birth following assisted reproductive technologies (ART) several decades ago, the global population of ART-conceived children has surpassed 13 million, with over 40,000 born in Kazakhstan. Despite this growth, questions remain about their long-term neurological outcomes, with existing studies reporting inconsistent findings. This study aimed to assess psychomotor development and the prevalence of nervous system pathologies among ART-conceived children in Kazakhstan and to develop a prognostic model for identifying pathological neurodevelopmental conditions. Methods: We studied 252 children (120 conceived via ART and 132 controls) using clinical examination and medical history data. Brain immaturity predictors were identified by univariate and multivariate logistic regression. Results: ART-conceived children exhibited a higher incidence of neurosonographic signs of brain structure immaturity. However, multivariate analysis indicated that ART itself was not an independent risk factor. Instead, perinatal complications—including prematurity, multiple pregnancy, low birth weight, asphyxia, and intrauterine infections—explained the observed differences. The prognostic model highlighted prematurity and preconceptional progesterone therapy as significant predictors. Overall neurological development did not differ significantly between the groups. Conclusions: These findings underscore the importance of early identification of perinatal risk factors and targeted preventive interventions to mitigate adverse neurodevelopmental outcomes in ART-conceived children. Full article

(This article belongs to the Special Issue Maternal-Fetal and Neonatal Medicine)

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12 pages, 236 KB

Open AccessReview

Advancing Precision in Neuro-Oncology with Intraoperative Imaging and Fluorescence Guidance: A Narrative Review

by Małgorzata Podstawka, Anna Dębska, Bartosz Szmyd, Karol Zaczkowski, Michał Piotrowski, Ernest J. Bobeff, Paweł Ratajczyk, Dariusz J. Jaskólski and Karol Wiśniewski

Biomedicines 2025, 13(10), 2550; https://doi.org/10.3390/biomedicines13102550 - 20 Oct 2025

Viewed by 858

Abstract

Malignant gliomas remain among the most formidable challenges in neuro-oncology, given their high morbidity and rising incidence worldwide. Surgical resection represents the cornerstone of treatment, typically followed by adjuvant radiotherapy and chemotherapy. Achieving maximal safe resection, however, requires advanced intraoperative guidance. A range [...] Read more.

Malignant gliomas remain among the most formidable challenges in neuro-oncology, given their high morbidity and rising incidence worldwide. Surgical resection represents the cornerstone of treatment, typically followed by adjuvant radiotherapy and chemotherapy. Achieving maximal safe resection, however, requires advanced intraoperative guidance. A range of adjuncts are currently employed, including 5-aminolevulinic acid (5-ALA), intraoperative ultrasound, computed tomography (iCT), and intraoperative magnetic resonance imaging (iMRI). More recently, an emerging technique—virtual MRI (vMRI)—has been developed, fusing intraoperative CT with preoperative high-resolution MRI to provide real-time, MRI-like updates of brain anatomy. Beyond imaging, tumour removal itself induces reorganization of eloquent brain networks, underscoring the critical need for precision tools that balance oncological control with preservation of neurological function. In this narrative review, we highlight and synthesize the evolving armamentarium of intraoperative technologies shaping the future of precision neuro-oncology. Full article

(This article belongs to the Section Neurobiology and Clinical Neuroscience)

2 pages, 588 KB

Open AccessCorrection

Correction: Damiański et al. Pathway to Remission in Severe Asthma: Clinical Effectiveness and Key Predictors of Success with Benralizumab Therapy: A Real-Life Study. Biomedicines 2025, 13, 887

by Piotr Damiański, Adam Jerzy Białas, Marta Kołacińska-Flont, Anna Elgalal, Katarzyna Jarmakowska, Dorota Kierszniewska, Michał Panek, Grzegorz Kardas, Piotr Kuna and Maciej Kupczyk

Biomedicines 2025, 13(10), 2549; https://doi.org/10.3390/biomedicines13102549 - 20 Oct 2025

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Abstract

In the original publication [...] Full article

(This article belongs to the Special Issue Molecular Targets for Biological Therapies of Severe Asthma: Second Edition)

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17 pages, 1165 KB

Open AccessSystematic Review

The Optimal Type and Dose of Exercise Interventions on VEGF Levels in Healthy Individuals, as Well as Obesity and Chronic Disease Populations: A Network Meta-Analysis

by Liqun Jiang, Huimin Ding, Dongjun Lee and Buongo Chun

Biomedicines 2025, 13(10), 2548; https://doi.org/10.3390/biomedicines13102548 - 19 Oct 2025

Viewed by 738

Abstract

Background/Objectives: Impaired angiogenesis and vascular dysfunction are central features of chronic diseases such as cardiovascular disorders, neurodegeneration, and metabolic syndrome. Vascular endothelial growth factor (VEGF) plays a pivotal role in vascular repair and metabolic regulation, yet its responses to exercise remain inconsistently [...] Read more.

Background/Objectives: Impaired angiogenesis and vascular dysfunction are central features of chronic diseases such as cardiovascular disorders, neurodegeneration, and metabolic syndrome. Vascular endothelial growth factor (VEGF) plays a pivotal role in vascular repair and metabolic regulation, yet its responses to exercise remain inconsistently reported. This study aimed to systematically compare the effects of different exercise modalities and doses on VEGF levels across diverse populations. Methods: This review was registered in PROSPERO (CRD42025643709) and followed PRISMA guidelines. PubMed, Web of Science, Embase, and Cochrane Library were searched until 16 January 2025. Eligible studies were randomized or quasi-experimental trials reporting exercise-induced changes in serum/plasma VEGF. Data were extracted and assessed independently using JBI tools. Exercise types were categorized and doses standardized as metabolic equivalents (METs). Network meta-analysis was performed in Stata17.0 (SMD as effect size), with SUCRA used for ranking. Dose–response relationships were examined by meta-regression (remr package), and publication bias was assessed via funnel plots. Results: Twenty-eight studies (N = 1138) were included. In healthy adults, lower-limb resistance training produced the greatest VEGF increase, with benefits observed above ~600 METs-min/week and peaking near 1950 METs-min/week. Among obese individuals, combined aerobic and resistance training under hypoxic conditions showed the highest VEGF response, though dose-specific effects were not significant. In patients with chronic conditions, upper-limb resistance training within 756–950 METs-min/week was most effective, displaying a U-shaped dose–response relationship. No substantial publication bias was detected. Conclusions: The VEGF response to exercise appears to be influenced by both population characteristics and training dosage. High-intensity lower-limb resistance training may provide greater benefits for healthy adults, while obese individuals might experience enhanced responses with combined training under hypoxic conditions. For clinical populations, moderate-dose upper-limb resistance training may be particularly beneficial. Large-scale, long-term trials are needed to further clarify and refine exercise prescriptions targeting VEGF-mediated vascular adaptations. Full article

(This article belongs to the Special Issue Mechanisms and Novel Therapeutic Approaches for Neurodegenerative Diseases (2nd Edition))

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17 pages, 1585 KB

Open AccessArticle

Short-Term Cyclosporin A Treatment Reduced Serum Neurofilament-Light Levels in Diffuse but Not Focal Traumatic Brain Injury in a Piglet Model

by Colin M. Huber, Akshara D. Thakore, Anna Oeur and Susan S. Margulies

Biomedicines 2025, 13(10), 2547; https://doi.org/10.3390/biomedicines13102547 - 18 Oct 2025

Viewed by 493

Abstract

Background/Objectives: Traumatic brain injury (TBI) in the pediatric patient results in acute neurophysiological deficits and can have potential long-term sequelae, impacting neurodevelopment. Serum biomarkers are an active area of study for TBI prognosis and diagnosis. Cyclosporin A (CsA), an immunosuppressant drug with [...] Read more.

Background/Objectives: Traumatic brain injury (TBI) in the pediatric patient results in acute neurophysiological deficits and can have potential long-term sequelae, impacting neurodevelopment. Serum biomarkers are an active area of study for TBI prognosis and diagnosis. Cyclosporin A (CsA), an immunosuppressant drug with neuroprotective qualities, targets mitochondria to stabilize the neurometabolic energy crisis following TBI. The objective of this study was to determine the acute effect of CsA treatment following focal and diffuse TBI on piglet serum biomarkers associated with glial neurofilaments, axonal dysfunction, and neuronal injury. Methods: Biomarker concentrations of GFAP, Nf-L, and UCH-L1 were quantified retrospectively from porcine serum samples (n = 488) at multiple timepoints from three experimental groups: anesthetized sham (n = 10), controlled cortical impact (CCI, n = 49), or rapid, non-impact rotations (RNR, n = 151) of the head. Injured animals received 24 h post-injury intravenous administration of saline or one of four CsA treatment doses (10, 20, 40, or 60 mg/kg/day), and then, were sacrificed. Results: After RNR, GFAP levels significantly increased from baseline at 1 h and recovered by 1 day to healthy reference ranges, while Nf-L increased at 1 day. Multiple CsA treatment doses (10, 40 mg/kg/day) significantly reduced Nf-L levels at 1 day compared to the untreated group. After CCI, GFAP and Nf-L increased at 1 day; there were no significant treatment effects. Conclusions: Focal and diffuse brain injury mechanisms resulted in distinct biomarker timelines. CsA reduced Nf-L levels at 1 day after diffuse TBI, showing promise of acute therapeutic benefit and warranting further investigation in extended timelines. Full article

(This article belongs to the Special Issue Mechanisms and Therapeutic Strategies of Brain and Spinal Cord Injury)

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24 pages, 3207 KB

Open AccessArticle

Reevaluating C-Reactive Protein for Perioperative Risk Stratification: The Overlooked Role of Sleep Apnea in Cardiac Surgery Outcomes

by Andrei Raul Manzur, Caius Glad Streian, Ana Lascu, Maria Alina Lupu, Horea Bogdan Feier and Stefan Mihaicuta

Biomedicines 2025, 13(10), 2546; https://doi.org/10.3390/biomedicines13102546 - 18 Oct 2025

Viewed by 665

Abstract

Background/Objectives: C-reactive protein (CRP) is widely used as a marker of perioperative inflammation, but its predictive value for cardiac surgical outcomes remains uncertain. Obstructive sleep apnea (OSA), a prevalent and underrecognized comorbidity, may independently contribute to postoperative complications through non-inflammatory mechanisms. This study [...] Read more.

Background/Objectives: C-reactive protein (CRP) is widely used as a marker of perioperative inflammation, but its predictive value for cardiac surgical outcomes remains uncertain. Obstructive sleep apnea (OSA), a prevalent and underrecognized comorbidity, may independently contribute to postoperative complications through non-inflammatory mechanisms. This study aimed to reevaluate the prognostic role of CRP and determine the clinical impact of OSA severity on postoperative recovery, focusing on new-onset atrial fibrillation (AF), prolonged intubation time, and postoperative CPAP/AIRVO use as indicators of respiratory burden. Methods: In this prospective cohort of 142 elective cardiac surgery patients, preoperative polysomnography and serial CRP measurements were obtained. Multivariable regression, mediation analysis, and propensity score matching (PSM) were performed to evaluate associations between OSA severity, CRP, and perioperative outcomes (AF, intubation time, CPAP/AIRVO use). Results: OSA severity independently predicted prolonged intubation (β = 1.74, p = 0.0019) and new-onset AF (β = 0.85, p = 0.004), even after excluding patients with preexisting arrhythmia. CRP showed poor discriminatory power as a standalone biomarker (AUC for IOT > 14 h = 0.445) and did not mediate OSA–outcome associations. However, CRP > 2.1 mg/dL doubled the odds of moderate-to-severe OSA (OR = 2.05, p = 0.041). A composite score integrating AHI, BMI, and postoperative CRP strongly correlated with postoperative respiratory support (p < 0.0001). Conclusions: OSA exerts a stronger and more consistent influence on perioperative outcomes than CRP, challenging reliance on CRP for risk stratification. Incorporating objective OSA screening and spirometry into preoperative assessment may enhance perioperative risk prediction and guide personalized management strategies. Full article

(This article belongs to the Special Issue Obstructive Sleep Apnea: Mechanisms, Comorbidities, and Optimization of Emerging and Established Therapies)

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45 pages, 3535 KB

Open AccessReview

CAR-T Cell Therapy for Prostate Cancer: Current Advances and Future Perspectives

by Maria Luisa Calabrò, Roberta Ettari, Carla Di Chio, Fabiola De Luca, Santo Previti and Maria Zappalà

Biomedicines 2025, 13(10), 2545; https://doi.org/10.3390/biomedicines13102545 - 18 Oct 2025

Viewed by 1715

Abstract

Prostate cancer is the most frequently diagnosed solid-organ malignancy in men worldwide. Metastatic castration-resistant prostate cancer represents a rapidly fatal, end-stage form of the disease for which current therapies remain palliative rather than curative. The advent of chimeric antigen receptor (CAR) T-cell therapy [...] Read more.

Prostate cancer is the most frequently diagnosed solid-organ malignancy in men worldwide. Metastatic castration-resistant prostate cancer represents a rapidly fatal, end-stage form of the disease for which current therapies remain palliative rather than curative. The advent of chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment of refractory hematologic malignancies, and a growing number of studies are now exploring its potential in solid tumors. In this review, we first provide a concise overview of current immunotherapeutic strategies for prostate cancer, including checkpoint inhibitors, vaccine-based approaches, and bispecific antibodies. We then focus on the most recent and promising developments in CAR-T cell therapy for this malignancy. Specifically, we examine the key tumor-associated antigens targeted in prostate cancer-directed CAR-T cell therapy and summarize findings from preclinical research as well as ongoing and completed clinical trials. Finally, we discuss the main challenges that limit the efficacy of CAR-T therapy in prostate cancer, such as antigen heterogeneity, immunosuppressive tumor microenvironments, on-target/off-tumor toxicity, limited T-cell persistence, and inefficient trafficking to metastatic lesions, and outline potential strategies to overcome these barriers. Our aim is to define a translational roadmap for advancing CAR-T therapy toward clinical application in patients with metastatic castration-resistant prostate cancer. Full article

(This article belongs to the Special Issue Diagnostic and Therapeutic Challenges of CAR-T Cell Therapy)

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Biomedicines, Volume 13, Issue 10 (October 2025) – 256 articles

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