Biomedicines

14 pages, 1477 KB

Open AccessArticle

Mammographic Calcifications in Lung Transplant Recipients: Prevalence and Evolution

by Jonathan Saenger, Jasmin Happe, Caroline Maier, Bjarne Kerber, Ela Uenal, Denise Bos, Thomas Frauenfelder and Andreas Boss

Biomedicines 2025, 13(9), 2318; https://doi.org/10.3390/biomedicines13092318 - 22 Sep 2025

Abstract

Objective: To investigate the prevalence and progression of macrocalcifications or sporadic scattered microcalcifications, breast arterial calcifications (BAC) and grouped microcalcifications in women undergoing lung transplantation (LTX). Materials and Methods: In this retrospective single-center cohort study, 176 adult female patients who underwent mammography between [...] Read more.

Objective: To investigate the prevalence and progression of macrocalcifications or sporadic scattered microcalcifications, breast arterial calcifications (BAC) and grouped microcalcifications in women undergoing lung transplantation (LTX). Materials and Methods: In this retrospective single-center cohort study, 176 adult female patients who underwent mammography between 2008 and 2025 were included: 82 LTX recipients and 94 age-matched controls. Mammographic findings were assessed using standardized BI-RADS criteria and a visual BAC scoring system. Clinical and demographic data were extracted from electronic medical records. Multivariable logistic regression and cumulative incidence analysis were used to evaluate associations and progression patterns. Interobserver agreement was assessed using Fleiss’ kappa. Results: BAC and grouped microcalcifications were significantly more prevalent in the LTX group in the last mammography (BAC: OR 6.57, 95% CI 2.34–20.7; microcalcifications: OR 14.6, 95% CI 3.93–73.9; both p < 0.001). Cumulative incidence analysis showed accelerated progression of BAC and grouped microcalcifications in LTX recipients (p ≤ 0.01), while macrocalcifications or sporadic scattered microcalcification progression did not differ significantly. BAC was often more extensive and potentially mimicked malignant findings. Interobserver agreement was highest for the four-level BAC scoring system (κ = 0.61), followed by BAC presence (κ = 0.59) and macrocalcifications (κ = 0.51), while grouped microcalcifications showed only fair agreement (κ = 0.33). Conclusions: Lung transplant recipients demonstrate significantly higher prevalence and faster progression of BAC and grouped microcalcifications compared to controls, complicating mammographic interpretation. Given their elevated risk of aggressive malignancies and diagnostic overlap between benign and suspicious calcifications, transplant recipients may benefit from tailored screening strategies. Full article

(This article belongs to the Special Issue Imaging Technology for Human Diseases)

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19 pages, 630 KB

Open AccessArticle

The Diagnostic Role of Novel Echocardiography Indices and Arterial Stiffness in Diabetic Cardiomyopathy

by Elina Khattab, Stefanos Sokratous, Michaela Kyriakou, Georgios Parpas, Ioannis Korakianitis, Paraskevi Papakyriakopoulou and Nikolaos P. E. Kadoglou

Biomedicines 2025, 13(9), 2317; https://doi.org/10.3390/biomedicines13092317 - 22 Sep 2025

Abstract

Background/Objectives: Diabetic cardiomyopathy (DBCM) is characterized by cardiac dysfunction in the absence of ischemic heart disease, hypertension, or valvular disease, often manifesting as heart failure with preserved ejection fraction (HFpEF). Early recognition of DBCM is clinically important, as it enables timely initiation [...] Read more.

Background/Objectives: Diabetic cardiomyopathy (DBCM) is characterized by cardiac dysfunction in the absence of ischemic heart disease, hypertension, or valvular disease, often manifesting as heart failure with preserved ejection fraction (HFpEF). Early recognition of DBCM is clinically important, as it enables timely initiation of tailored therapies and may slow down the progression to overt heart failure with reduced ejection fraction (HFrEF). This study aimed to evaluate the diagnostic utility of advanced echocardiographic techniques—myocardial work (MW), diastolic stress echocardiography (DSTE), Cardio-Ankle Vascular Index (CAVI)—and selected serum biomarkers in identifying DBCM. Methods: In this prospective observational study with 12-month follow-up, 125 diabetic patients with preserved ejection fraction and symptoms of HF or recent HF hospitalization were enrolled. Using the Heart Failure Association Pre-test Probability of HFpEF criteria, 37 were classified as DBCM-HFpEF and 88 as diabetic controls. An additional 47 age- and sex-matched non-diabetic individuals served as controls. All participants underwent resting echocardiography (MW, GLS), DSTE, CAVI assessment, and biomarker measurement (BNP, troponin, galectin-3). Results: Compared to non-diabetics, diabetic patients had significantly higher TRVmax (2.21 vs. 2.05 m/s), LAVI (39.70 vs. 33.50 mL/m²), E/e′ (8.64 vs. 7.59), CAVI (8.51 vs. 7.82 m/s), BNP (91.50 vs. 35.10 pg/mL), and troponin (3.94 vs. 2.43 ng/mL) (all p < 0.01), while galectin-3 levels showed no significant difference between groups. Differences were more pronounced between DBCM and No-DBCM diabetic groups. Multivariate analysis identified BNP (OR 5.45), TRVmax (OR 8.56), and CAVI (OR 1.91) as independent predictors of DBCM. Conclusions: DSTE and CAVI, alongside BNP and echocardiographic parameters, may provide valuable noninvasive tools for the early detection of DBCM in diabetic patients presenting with otherwise unexplained dyspnea, potentially enabling earlier intervention and improved outcomes. This is clinically important guiding an efficient management of an increasing number of diabetic patients presented with unexplained dyspnea. Full article

(This article belongs to the Section Endocrinology and Metabolism Research)

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25 pages, 1839 KB

Open AccessSystematic Review

Comparative Efficacy of Platelet-Rich Plasma, Autologous Serum, and Artificial Tears in Dry Eye Disease: A Systematic Review and Meta-Analysis

by Alexandra Laura Mederle, Diana Andrei, Laura Andreea Ghenciu, Emil Robert Stoicescu, Roxana Iacob and Ovidiu Alin Haţegan

Biomedicines 2025, 13(9), 2316; https://doi.org/10.3390/biomedicines13092316 - 22 Sep 2025

Abstract

Background/Objectives: Dry eye disease (DED) is a prevalent, complex disorder with a major impact on patients’ quality of life. While artificial tears (AT) are still the first-line treatment, their effectiveness is often limited in moderate-to-severe cases. Autologous serum (AS) and platelet-rich plasma [...] Read more.

Background/Objectives: Dry eye disease (DED) is a prevalent, complex disorder with a major impact on patients’ quality of life. While artificial tears (AT) are still the first-line treatment, their effectiveness is often limited in moderate-to-severe cases. Autologous serum (AS) and platelet-rich plasma (PRP) are now recognized as viable biologic treatments due to their regenerative and anti-inflammatory characteristics. This systematic review and meta-analysis sought to assess and compare the clinical efficacy of PRP, AS, and AT in the treatment of DED, with a focus on comparative studies. Methods: A comprehensive search of PubMed, Scopus, and Google Scholar was conducted until June 2025 for studies directly comparing PRP, AS, and AT. Eligible trials included patients with DED who reported results such as the Schirmer test, tear break-up time (TBUT), and Ocular Surface Disease Index (OSDI). The risk of bias was calculated using ROB 2 for randomized trials and ROBINS-I for non-randomized studies. Meta-analyses were carried out using standardized mean differences (SMDs) and 95% confidence intervals (CIs). Results: Seventeen studies were included in the systematic review. Both PRP and AS demonstrated greater improvements in OSDI, TBUT, and Schirmer test scores compared to AT. PRP showed a trend toward better outcomes than AS, especially in studies using injectable PRP. However, substantial heterogeneity and methodological variability were noted. Conclusions: Comparative research suggests that PRP and AS are more effective than AT in treating DED. Direct comparisons of PRP and AS yield varied results, with the route of delivery impacting outcomes. Given the heterogeneity of current protocols, further standardized, long-term trials are required to confirm the optimal delivery method and ensure safety. Full article

(This article belongs to the Special Issue Recent Research on Dry Eye)

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16 pages, 538 KB

Open AccessReview

Heparin Binding Protein in Sepsis—A Comprehensive Overview of Pathophysiology, Clinical Usage and Utility as Biomarker

by Foteini Tasouli, Eleni Georgopoulou, Christodoulos Chatzigrigoriadis, Dimitrios Velissaris and Christos Michailides

Biomedicines 2025, 13(9), 2315; https://doi.org/10.3390/biomedicines13092315 - 22 Sep 2025

Abstract

The heparin-binding protein (HBP) is an enzymatically inactive protein of the serine protease family that plays an important role in host response to stress, especially infection and sepsis. It is produced by activated neutrophils due to a variety of stimuli and is part [...] Read more.

The heparin-binding protein (HBP) is an enzymatically inactive protein of the serine protease family that plays an important role in host response to stress, especially infection and sepsis. It is produced by activated neutrophils due to a variety of stimuli and is part of the immune response that leads to macrophage, lymphocyte, and neutrophil activation and monocyte adhesion. Its most common repository is the azurophilic granules of the neutrophils. HBP has been studied as a biomarker for several infections, including central nervous system infection, respiratory tract infection, and urinary tract infection, and in several settings, including the Emergency Department and Intensive Care Unit, with promising results. As a biomarker for infection and sepsis, HBP has been compared to other commonly used biomarkers such as Neutrophil to Lymphocyte Ratio, White Blood Count, C-reactive protein, and Procalcitonin, with at least comparable performance. Its sharp increase is promising for the early detection of sepsis. The ability to differentiate inflammatory conditions from infections and bacterial from non-bacterial causes of infection has also been demonstrated. The sepsis-related organ damage, as it is represented by the Sequential Organ Failure Assessment score, can also be reflected by the proportional increase in HBP. Consequently, HBP could be a helpful and promising biomarker for sepsis and infection. Full article

(This article belongs to the Special Issue Microbial Infections and Sepsis: Pathophysiological Mechanisms and Therapeutic Approaches)

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18 pages, 871 KB

Open AccessReview

Allogeneic NKG2D CAR-T Cell Therapy: A Promising Approach for Treating Solid Tumors

by Sabir A. Mukhametshin, Elvina M. Gilyazova, Damir R. Davletshin, Irina A. Ganeeva, Ekaterina A. Zmievskaya, Vitaly V. Chasov, Alexsei V. Petukhov, Aigul Kh. Valiullina, Sheila Spada and Emil R. Bulatov

Biomedicines 2025, 13(9), 2314; https://doi.org/10.3390/biomedicines13092314 - 22 Sep 2025

Abstract

Chimeric Antigen Receptor (CAR)-T cell therapy has transformed the treatment landscape of cancer, yet major challenges remain in enhancing efficacy, reducing adverse effects, and expanding accessibility. Autologous CAR-T cells, derived from individual patients, have achieved remarkable clinical success in hematologic malignancies; however, their [...] Read more.

Chimeric Antigen Receptor (CAR)-T cell therapy has transformed the treatment landscape of cancer, yet major challenges remain in enhancing efficacy, reducing adverse effects, and expanding accessibility. Autologous CAR-T cells, derived from individual patients, have achieved remarkable clinical success in hematologic malignancies; however, their highly personalized nature limits scalability, increases costs, and delays timely treatment. Allogeneic CAR-T cells generated from healthy donors provide an “off-the-shelf” alternative but face two critical immune barriers: graft-versus-host disease (GvHD), caused by donor T-cell receptor (TCR) recognition of host tissues, and host-versus-graft rejection, mediated by recipient immune responses against donor HLA molecules. Recent advances in genome engineering, particularly Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9, allow precise modification of donor T cells to overcome these limitations. For example, TRAC gene knockout eliminates TCR expression, preventing GvHD, while disruption of HLA molecules reduces immunogenicity without impairing cytotoxicity. Beyond hematologic cancers, CRISPR-edited allogeneic CAR-T cells targeting the NKG2D receptor have shown promise in preclinical studies and early-phase trials. NKG2D CAR-T cells recognize stress ligands (MICA/B, ULBP1–6) expressed on over 80% of diverse solid tumors, including pancreatic and ovarian cancers, thereby broadening therapeutic applicability. Nevertheless, the genomic editing process carries risks of off-target effects, including potential disruption of tumor suppressor genes and oncogenes, underscoring the need for stringent safety and quality control. This review examines the distinguishing features of allogeneic versus autologous CAR-T therapy, with a particular focus on NKG2D-based allogeneic CAR-T approaches for solid tumors. We summarize current strategies to mitigate immune barriers, discuss practical manufacturing challenges, and analyze available clinical data on NKG2D CAR-T trials. Collectively, these insights underscore both the promise and the hurdles of developing safe, universal, and scalable allogeneic CAR-T therapies for solid malignancies. Full article

(This article belongs to the Special Issue Novel Progress in Cancer Immunotherapy)

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7 pages, 198 KB

Open AccessEditorial

Human Stem Cells in Disease Modelling and Treatment: Bridging the Gap Between Bench and Bedside

by Alvaro Plaza Reyes and Sofia M. Calado

Biomedicines 2025, 13(9), 2313; https://doi.org/10.3390/biomedicines13092313 - 22 Sep 2025

Abstract

Human stem cell research is entering a stage where disease modeling, translational applications, and clinical therapies are increasingly connected. This editorial provides an overview of the contributions included in this Special Issue, titled “Human Stem Cells in Disease Modelling and Treatment”, placing them [...] Read more.

Human stem cell research is entering a stage where disease modeling, translational applications, and clinical therapies are increasingly connected. This editorial provides an overview of the contributions included in this Special Issue, titled “Human Stem Cells in Disease Modelling and Treatment”, placing them within the wider landscape of stem cell science. We summarize advances in ovarian stem cells for infertility, mesenchymal stem cells for neurodegeneration, pluripotent stem cell-derived cardiovascular and kidney organoids, adipose-derived stem cells, and emerging immunomodulatory and neural progenitor approaches. These studies illustrate the breadth of stem cell research and its potential to inform clinical practice. At the same time, challenges remain in reproducibility, safety, scalability, and ethical oversight. Looking forward, collaborative work and harmonized global standards will be important to bring laboratory findings into therapies that are safe, effective, and accessible. This editorial closes the first edition of the Special Issue with a reflection on current progress and directions for the future. Full article

(This article belongs to the Special Issue Human Stem Cells in Disease Modelling and Treatment)

15 pages, 2435 KB

Open AccessArticle

Localization and Expression of Renin–Angiotensin System Receptors in Lung from Transplant Patients: A Case-Control Study

by Andresa Thomé Silveira, Lucas Sagrillo Fagundes, Juliane Flor, Isabel Amaral Martins, Laura Bastos Otero, Laura Tibola Marques da Silva, Lorenzo Santana Maciel, Sarah Eller, Giuliano Rizzotto Guimarães, Fabíola Adelia Perin, Márcia Rosângela Wink and Katya Rigatto

Biomedicines 2025, 13(9), 2312; https://doi.org/10.3390/biomedicines13092312 - 21 Sep 2025

Abstract

Objective: We aimed to assess the expression and localization of renin-angiotensin system (RAS) receptors in lung tissue and the plasma concentration of related peptides in IPF patients. Materials and Methods: This case–control study involved 19 patients from southern Brazil undergoing lung [...] Read more.

Objective: We aimed to assess the expression and localization of renin-angiotensin system (RAS) receptors in lung tissue and the plasma concentration of related peptides in IPF patients. Materials and Methods: This case–control study involved 19 patients from southern Brazil undergoing lung resection or transplantation. Plasma levels of Angiotensin I, II, A, 1-7, Alamandine were measured via liquid chromatography–tandem mass spectrometry. Lung tissue expression and localization of angiotensin type 1 (AT1), Mas, and Mas-related G-protein-coupled receptor D (MrgD) receptors were evaluated using Western blot and immunohistochemistry. Clinical data and the 6-min walk test were analyzed to correlate receptor expression with lung function and oxygen dependence. Results: IPF patients showed reduced forced vital capacity (FVC) at 49 ± 13% and forced expiratory volume (FEV1) at 51 ± 14%, with a 60% increase in oxygen dependence. Plasma peptide concentrations were similar between the groups, except for Angiotensin I, which was significantly higher in the control group. In IPF lungs, AT1 and Mas receptors were expressed 2.31 and 2.13 times more, respectively, while MrgD expression was lower. Mas receptors were mostly found in bronchiole areas, whereas MrgD was predominant in the lung parenchyma. Conclusions: This study indicates that the RAS operates independently within tissue, in addition to its systemic functions, highlighting distinct differences between tissue and plasma RAS activities. The distinct roles of MrgD and Mas receptors in lung structure and function could be pivotal for new therapies, potentially leading to more effective IPF treatments. Full article

(This article belongs to the Special Issue Navigating the Complex Landscape of Non-Communicable Respiratory Diseases: Emerging Challenges and Opportunities)

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12 pages, 1062 KB

Open AccessArticle

by Alexander Lukas Rattunde, Vitus André Knecht and Eckart Bertelmann

Biomedicines 2025, 13(9), 2311; https://doi.org/10.3390/biomedicines13092311 - 21 Sep 2025

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Abstract

Objective: IgG4-Related Orbital Disease (IgG4-ROD) is an incompletely understood differential of idiopathic orbital inflammatory syndrome (IOIS). Accurate separation guides therapy and prognosis. This retrospective study also profiles its clinical features, therapy needs, and compares them with IOIS. Methodology: Fifty-four patients were biopsied between [...] Read more.

Objective: IgG4-Related Orbital Disease (IgG4-ROD) is an incompletely understood differential of idiopathic orbital inflammatory syndrome (IOIS). Accurate separation guides therapy and prognosis. This retrospective study also profiles its clinical features, therapy needs, and compares them with IOIS. Methodology: Fifty-four patients were biopsied between January 2016 and December 2023, comprising 18 who were diagnosed with IgG4-ROD (4 definite, 14 probable) and 36 with IOIS. Mean follow-up was 21.7 ± 26.2 months for IgG4-ROD versus 7.5 ± 10.3 months for IOIS. Results: Patients with IgG4-ROD were older than those with IOIS (mean 61.8 vs. 49.9 years). Gender distribution was balanced. The lacrimal gland (66.7% vs. 61.6%; p = 0.690) and extra-ocular muscles (55.6% vs. 30.6%; p = 0.076) were frequently involved in both entities, whereas paranasal sinus infiltration was significantly associated with IgG4-ROD (p = 0.003). Common shared symptoms (p > 0.05) included eyelid swelling (83.3% vs. 86.1%), exophthalmos (50% vs. 36.1%), and motility restriction (22.2% vs. 25%). Relative afferent pupillary defect (p = 0.042), chemosis (p = 0.02), and systemic disease (p = 0.005) were more prevalent in IgG4-ROD. During ≥ 6-month follow-up (n = 7), only 28.6% of IgG4-ROD patients achieved sustained remission; Kaplan–Meier analysis yielded a mean time to first event of 926 days. Additional steroid-sparing therapy was required more often in IgG4-ROD than in IOIS (p = 0.002). Conclusion: IgG4-ROD and IOIS share clinical features but differ in key aspects such as associated diseases, therapy requirements, and disease control. Understanding these differences is crucial for targeted diagnostics and individualized treatment strategies. Full article

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

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16 pages, 1097 KB

Open AccessArticle

The Role of Antifibrotic Therapy in Pulmonary Fibrosis and Lung Cancer: A Multicenter Retrospective Analysis

by Francesco Rocco Bertuccio, Nicola Baio, Fabio Perrotta, Donato Lacedonia, Vito D’Agnano, Andrea Bianco, Giulia Scioscia, Pasquale Tondo, Maria Pia Foschino Barbaro, Chandra Bortolotto, Angelo Guido Corsico and Giulia Maria Stella

Biomedicines 2025, 13(9), 2310; https://doi.org/10.3390/biomedicines13092310 - 21 Sep 2025

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Abstract

Background: Patients with fibrotic interstitial lung disease (ILD) are at increased risk of lung cancer, yet the impact of antifibrotic therapy on oncologic outcomes remains unclear. Objective: This study aimed to explore associations between antifibrotic therapy and overall survival (OS) and acute [...] Read more.

Background: Patients with fibrotic interstitial lung disease (ILD) are at increased risk of lung cancer, yet the impact of antifibrotic therapy on oncologic outcomes remains unclear. Objective: This study aimed to explore associations between antifibrotic therapy and overall survival (OS) and acute exacerbations of ILD (AE-ILD) in patients with fibrotic ILD who develop lung cancer. Methods: We retrospectively analyzed 61 patients from multiple Italian centers: 35 received antifibrotic therapy (pirfenidone or nintedanib) and 26 did not. Outcomes included OS from cancer diagnosis and post-treatment AE-ILD. Results: Mean OS was 17.9 months in the antifibrotic group and 33.2 months in the non-antifibrotic group; no adjusted survival analyses were possible due to missing censoring data, and these descriptive values should not be overinterpreted. AE-ILD occurred in 11.4% of antifibrotic-treated patients and 11.5% of those without antifibrotics. PD-L1 expression was detected in 24.1% vs. 21.8% of tumors in the two groups, and autoantibody positivity was observed in 22.8% vs. 30.7%, respectively, reflecting differences in ILD subtypes. Conclusions: In this heterogeneous real-world cohort, antifibrotic therapy was not associated with increased AE-ILD risk, and descriptive OS comparisons showed no clear survival advantage. These exploratory findings warrant confirmation in larger, prospective studies. Full article

(This article belongs to the Special Issue Thoracic Malignancies: From Pathophysiology to Novel Therapeutic Approaches)

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26 pages, 1204 KB

Open AccessReview

A Clinical Review of the Connections Between Diabetes Mellitus, Periodontal Disease, and Cardiovascular Pathologies

by Otilia Țica, Ioana Romanul, Gabriela Ciavoi, Vlad Alin Pantea, Ioana Scrobota, Lucian Șipoș, Cristian Marius Daina and Ovidiu Țica

Biomedicines 2025, 13(9), 2309; https://doi.org/10.3390/biomedicines13092309 - 20 Sep 2025

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Abstract

Background: Diabetes mellitus (DM), periodontal disease (PD), and cardiovascular disease (CVD) are highly prevalent global health conditions with overlapping pathophysiological mechanisms. Emerging evidence suggests a bidirectional and synergistic relationship among them, driven by chronic inflammation, immune dysregulation, oxidative stress, and microbial dysbiosis. [...] Read more.

Background: Diabetes mellitus (DM), periodontal disease (PD), and cardiovascular disease (CVD) are highly prevalent global health conditions with overlapping pathophysiological mechanisms. Emerging evidence suggests a bidirectional and synergistic relationship among them, driven by chronic inflammation, immune dysregulation, oxidative stress, and microbial dysbiosis. Objective: This review synthesizes current literature on the interconnectedness of DM, PD, and CVD, emphasizing shared molecular pathways, clinical implications, and opportunities for integrated management. Methods: A systematic review and narrative synthesis of recent clinical trials, observational studies, and multi-omics investigations was conducted to explore the mechanisms linking these three conditions. A structured literature search was performed across PubMed, Scopus, and Web of Science from database inception until 30 June 2025. Key findings were contextualized within systems biology, precision medicine, and real-world clinical strategies. Results: DM exacerbates periodontal inflammation and accelerates tissue destruction via hyperglycemia-induced inflammatory mediators, while periodontitis worsens glycemic control and insulin resistance. Both conditions independently elevate cardiovascular risk, and their co-occurrence significantly amplifies the incidence of adverse cardiovascular events. Shared biomarkers such as Interleukin (IL)-6, Tumor Necrosis Factor (TNF)-α, and CRP, as well as overlapping genetic and epigenetic signatures, underscore a common inflammatory axis. Periodontal therapy has demonstrated modest but meaningful benefits on glycemic control and endothelial function, while cardiometabolic therapies (e.g., statins, Glucagon-Like Peptide (GLP-1) receptor agonists, SGLT2 inhibitors) show potential to improve periodontal outcomes. Probiotics, microbiome-targeted therapies, and AI-based risk models are emerging as future tools. Conclusions: DM, PD, and CVD form a mutually reinforcing triad mediated by systemic inflammation and metabolic dysregulation. Integrated, multidisciplinary care models and precision health strategies are essential to address this inflammatory burden and improve long-term outcomes. Further large-scale interventional trials and mechanistic human studies are needed to establish causal links and optimize combined therapeutic approaches. Full article

(This article belongs to the Special Issue Connections Between Diabetes Mellitus, Other Metabolic and Endocrine Dysfunctions and Cardiovascular Pathologies—Second Edition)

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34 pages, 1574 KB

Open AccessReview

Linking Metabolic Disorders and Immune System Phenomena in Schizophrenia: The Role of Adipose Tissue and Inflammation

by Aleksandra Julia Oracz, Mateusz Zwierz, Maciej Naumowicz, Stefan Modzelewski, Maria Suprunowicz and Napoleon Waszkiewicz

Biomedicines 2025, 13(9), 2308; https://doi.org/10.3390/biomedicines13092308 - 20 Sep 2025

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Abstract

Emerging evidence highlights the role of chronic low-grade inflammation and dysregulated cytokines in both obesity and schizophrenia, suggesting overlapping immune system pathways that contribute to cognition and nervous system inflammation. Excess adipose tissue functions as an active endocrine organ, releasing pro-inflammatory mediators that [...] Read more.

Emerging evidence highlights the role of chronic low-grade inflammation and dysregulated cytokines in both obesity and schizophrenia, suggesting overlapping immune system pathways that contribute to cognition and nervous system inflammation. Excess adipose tissue functions as an active endocrine organ, releasing pro-inflammatory mediators that may serve as potential biomarkers, while the use of antipsychotic agents in schizophrenia further modifies cytokine profiles and immune responses. A key knowledge gap lies in understanding how adipose-related inflammation modifies the severity of psychotic symptoms, cognitive deficits, and the efficacy of antipsychotic medications. This review aims to present excess adipose tissue as a potential contributor to the development of SCZ or a modifier of treatment efficacy, emphasizing the role of immune imbalance, inflammatory pathways, and metabolic dysfunction. By synthesizing current findings, we aim to present obesity not only as a frequent comorbidity in schizophrenia but also as a potential driver of neuroinflammation and disease progression. Here, we demonstrate that excess adiposity may perpetuate a vicious cycle linking metabolic dysfunction, immune activation, and psychiatric symptomatology. Situating these findings within a broader context, the review underscores the clinical need for inflammation-informed, individualized management strategies that integrate psychiatric care with metabolic monitoring. Ultimately, clarifying the shared inflammatory pathways of obesity and schizophrenia may open new avenues for biomarker development and targeted interventions. Full article

(This article belongs to the Special Issue Feature Reviews in Cytokines)

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19 pages, 5195 KB

Open AccessArticle

Key Common Genes with LTF and MMP9 Between Sepsis and Relapsed B-Cell Lineage Acute Lymphoblastic Leukemia in Children

by Ying-Ping Xiao, Yu-Cai Cheng, Chun Chen, Hong-Man Xue, Mo Yang and Chao Lin

Biomedicines 2025, 13(9), 2307; https://doi.org/10.3390/biomedicines13092307 - 20 Sep 2025

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Abstract

Background: Pediatric sepsis is a life-threatening disease that is associated with the progression of acute lymphoblastic leukemia (ALL) and the recurrence of B-cell ALL (B-ALL). Although previous studies have reported a partial association between sepsis and ALL, there is limited research on the [...] Read more.

Background: Pediatric sepsis is a life-threatening disease that is associated with the progression of acute lymphoblastic leukemia (ALL) and the recurrence of B-cell ALL (B-ALL). Although previous studies have reported a partial association between sepsis and ALL, there is limited research on the shared genes between pediatric sepsis and relapsed B-ALL. This study aims to further elucidate the more comprehensive and novel common genetic factors and molecular pathways between the two diseases. Methods: Gene expression datasets pertaining to pediatric sepsis (GSE13904, GSE80496) and relapsed B-ALL (GSE3910, GSE28460) were retrieved from the Gene Expression Omnibus database for this retrospective analysis. The initial analysis identified differentially expressed genes common to both pediatric sepsis and relapsed B-ALL. Subsequent investigations employed three complementary approaches: protein–protein interaction networks, molecular complex detection (MCODE) clustering functions, and support vector machine recursive feature elimination model to separately identify the diagnostic biomarkers for each condition. Importantly, key common genes were identified by overlapping the diagnostic genes for pediatric sepsis and relapsed B-ALL. Further characterization involved comprehensive functional analysis through the Metascape platform, construction of transcription factor (TF)-mRNA-microRNA (miRNA) networks, drug prediction, and molecular docking to explore their biological significance and potential therapeutic targets. Results: Comparative analysis of pediatric sepsis-related and relapsed B-ALL-related datasets revealed two shared genetic markers, lactotransferrin (LTF) and matrix metallopeptidase 9 (MMP9), exhibiting diagnostic significance and consistent upregulation in both disease groups. Transcriptional regulatory network analysis identified specificity protein 1 (SP1) as the principal transcription factor capable of coregulating LTF and MMP9 expression. In addition, molecular docking demonstrated high-affinity interactions between curcumin and MMP9 (−7.18 kcal/mol) as well as reserpine and LTF (−5.4 kcal/mol), suggesting their potential therapeutic utility for clinical evaluation. Conclusions: These findings elucidate the molecular pathogenesis involving LTF and MMP9 in pediatric sepsis and relapsed B-ALL, providing novel insights for clinical diagnosis and therapeutic development. Full article

(This article belongs to the Special Issue New Insights in Hematologic Malignancies: From Pathophysiologic Mechanisms to Therapeutic Strategies)

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14 pages, 439 KB

Open AccessArticle

Evaluating Cardio-Protective Molecules by Efficacy Based on Weight Reduction and HbA1c Targets

by Teodor Salmen, Valeria-Anca Pietrosel, Flaviana-Veronica Urzica, Diana-Elena Visan, Bianca-Margareta Salmen, Radu-Cristian Cimpeanu, Delia Reurean-Pintilei, Mihaela-Simona Popoviciu and Anca Pantea Stoian

Biomedicines 2025, 13(9), 2306; https://doi.org/10.3390/biomedicines13092306 - 20 Sep 2025

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Abstract

Background: The effectiveness of GLP-1 RAs and SGLT-2i classes, evaluated by a HbA1c target of <7% and body weight reduction (BWR) of 5% in patients with type 2 diabetes mellitus (T2DM), represents the aim of this article. Methods: A retrospective analysis [...] Read more.

Background: The effectiveness of GLP-1 RAs and SGLT-2i classes, evaluated by a HbA1c target of <7% and body weight reduction (BWR) of 5% in patients with type 2 diabetes mellitus (T2DM), represents the aim of this article. Methods: A retrospective analysis was conducted on consecutively admitted out-patients of a tertiary care center for diabetes mellitus (DM) treatment from Romania, where 405 enrolled patients were evaluated at baseline, 6-, and 12-month visits. Results: SGLT-2i were superior to GLP-1 RAs and metformin, providing higher rates of combined target achievements—22.7% at 12 months, p < 0.001. Both HbA1c reduction and BWR were more consistent at the 12-month visit: 6.58% for metformin, 22.68% for SGLT-2i, and 5.88% for GLP-1 Ras, as compared to baseline while the 12-month visit results were as follows: 4.79% for metformin, 5.04% for SGLT-2i and 5.88% for GLP-1 RAs as compared to the 6-month visit. Despite the fact that the HbA1c < 7% target at baseline was 38.92% for metformin, 17.64% for SGLT-2i, and 41.17% for GLP-1 RAs, BWR was achieved less, probably influenced by insulin treatment. Conclusions: This study shows real-world Romanian efficacy and over the time response of administering the new classes in T2DM patients when aiming for HbA1c < 7% levels and 5% BWR, with SGLT-2i outperforming metformin and GLP-1 RAs, emphasizing their growing role in the management of T2DM. Full article

(This article belongs to the Special Issue New Advances in Cardiovascular Drugs: In Memory of Professor Akira Endo)

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13 pages, 262 KB

Open AccessArticle

Bone Mineral Density in HIV-Infected People–the Experience of Craiova Regional Center

by Florentina Dumitrescu, Livia Dragonu, Eugenia-Andreea Marcu, Vlad Pădureanu, Andreea Cristina Stoian, Cristiana-Luiza Rădoi-Troacă, Rodica Pădureanu, Anca Duduveche, Ilona-Andreea Georgescu and Lucian Giubelan

Biomedicines 2025, 13(9), 2305; https://doi.org/10.3390/biomedicines13092305 - 20 Sep 2025

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Abstract

Background: Human Immunodeficiency Virus (HIV) is a virus that progressively impairs immune function by depleting CD4 + T-lymphocytes, ultimately leading to acquired immunodeficiency syndrome (AIDS). People living with HIV face a higher risk of developing various bone disorders, such as osteopenia, osteoporosis, and [...] Read more.

Background: Human Immunodeficiency Virus (HIV) is a virus that progressively impairs immune function by depleting CD4 + T-lymphocytes, ultimately leading to acquired immunodeficiency syndrome (AIDS). People living with HIV face a higher risk of developing various bone disorders, such as osteopenia, osteoporosis, and osteonecrosis. The aim of this study was to evaluate the bone mineral density (BMD) status, to determine the prevalence of osteopenia/osteoporosis and to identify the risk factors for low BMD in patients living with HIV undergoing antiretroviral treatment (ART), registered in Craiova Regional Center. Methods: A retrospective study was conducted between June 2024 and January 2025, including HIV-infected subjects aged over 18 years. Results: The study group included 106 patients. Dual-energy X-ray absorptiometry (DEXA) showed that 87 patients had low BMD, 51% having osteopenia and 31.1% having osteoporosis. We found a statistically significant correlation between low BMD and older age, higher levels HIV viremia, CD4 nadir < 200 cells/mm³, prolonged ART exposure and tenofovir disoproxil fumarate containing regimens. Conclusions: These findings support the inclusion of routine bone health monitoring in the standard care of patients with HIV, as well as the need for reevaluation. Full article

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

14 pages, 409 KB

Open AccessArticle

Clinical Implications of Bacteremia Caused by Non-baumannii Acinetobacter Compared with Those of Acinetobacter baumannii Bacteremia

by Jin Woong Suh, Ji Young Hong, Keun Ju Kim, Duck Jin Hong and Sun Bean Kim

Biomedicines 2025, 13(9), 2304; https://doi.org/10.3390/biomedicines13092304 - 20 Sep 2025

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Abstract

Objectives: This study aimed to compare clinical characteristics, antimicrobial susceptibility, and 28-day mortality between patients with Acinetobacter baumannii bacteremia (ABB) and non-baumannii Acinetobacter bacteremia (NBAB) after rapid matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) species identification. Methods: We retrospectively reviewed [...] Read more.

Objectives: This study aimed to compare clinical characteristics, antimicrobial susceptibility, and 28-day mortality between patients with Acinetobacter baumannii bacteremia (ABB) and non-baumannii Acinetobacter bacteremia (NBAB) after rapid matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) species identification. Methods: We retrospectively reviewed the clinical data of adult ABB and NBAB patients over >7 years. Multivariate logistic regression was used to identify the risk factors for 28-day mortality. Results: Of 273 episodes of Acinetobacter species bacteremia, 224 (82.1%) were ABB and 49 (17.9%) were NBAB. NBA isolates were predominantly A. nosocomialis (49%), with smaller proportions of A. bereziniae, A. junii, A. ursingii, and others. The primary sites of infection in NBAB cases were the intra-abdomen, urinary tract, intravascular catheters, and lungs. While only 4.0% of A. baumannii isolates were susceptible to carbapenem, 87.8% of non-baumannii Acinetobacter isolates were susceptible. Multivariate analysis revealed that low carbapenem resistance was independently associated with NBAB. Additionally, a higher Pitt bacteremia score, septic shock, continuous renal replacement therapy, inappropriate empirical antibiotic therapy, and thrombocytopenia were independent risk factors for the 28-day mortality in patients with ABB. Conclusions: Although less common than ABB, NBAB cases are increasing and exhibit lower carbapenem resistance. Rapid MALDI-TOF MS identification enables timely and appropriate antibiotic treatment. The key factors driving the 28-day mortality include illness severity, septic shock, renal replacement therapy, inappropriate antibiotics, and thrombocytopenia, highlighting the need for early risk assessments and tailored management. Ongoing surveillance and species-specific strategies are essential for combating resistant Acinetobacter infections. Full article

(This article belongs to the Special Issue Infectious Diseases: Prevention, Diagnosis, and Treatment Under Antimicrobial Resistance Global Urgency)

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2 pages, 134 KB

Open AccessEditorial

TAFRO Syndrome—A Decade Later, Still Racing Against Time

by Yasufumi Masaki

Biomedicines 2025, 13(9), 2303; https://doi.org/10.3390/biomedicines13092303 - 19 Sep 2025

Viewed by 128

Abstract

Since its first description in Japan in 2010 [...] Full article

(This article belongs to the Special Issue Diagnosis, Pathogenesis and Treatment of TAFRO Syndrome)

11 pages, 1112 KB

Open AccessArticle

Thoracic MRI in Pediatric Oncology: Feasibility and Image Quality of Post-Contrast Free-Breathing Radial 3D T1 Weighted Imaging

by Patricia Tischendorf, Marc-David Künnemann, Tobias Krähling, Jan Hendrik Lange, Walter Heindel and Laura Beck

Biomedicines 2025, 13(9), 2302; https://doi.org/10.3390/biomedicines13092302 - 19 Sep 2025

Viewed by 159

Abstract

Objectives: To compare the feasibility and image quality of a post-contrast free-breathing radial stack-of-stars 3D T1w turbo-field echo Dixon sequence (3D T1w VANE mDIXON) with a conventional cartesian breath-hold 3D T1w fast-field echo mDIXON sequence in pediatric oncology patients undergoing chest MRI. [...] Read more.

Objectives: To compare the feasibility and image quality of a post-contrast free-breathing radial stack-of-stars 3D T1w turbo-field echo Dixon sequence (3D T1w VANE mDIXON) with a conventional cartesian breath-hold 3D T1w fast-field echo mDIXON sequence in pediatric oncology patients undergoing chest MRI. Methods: A total of 48 children (34 females; mean age 5.3 ± 3.7 years) underwent contrast-enhanced chest MRI, with 24 examined using the 3D T1w VANE mDIXON sequence and 24 with a conventional breath-hold 3D T1w mDIXON sequence. Image quality was independently assessed by three radiologists using a 5-point scale. Signal-to-noise ratio (SNR) was measured at two anatomical sites, a homogeneous paraspinal muscle region (SNR_muscle) and the liver apex (SNR_liver), while avoiding vessels and signal inhomogeneities. The presence of respiratory artifacts, total imaging time, and the need for general anesthesia or sedation were recorded. Interobserver agreement was determined using Fleiss’s kappa (ϰ), and mean SNR values were compared between groups using an independent samples t-test. Results: The 3D T1w VANE mDIXON sequence yielded significantly higher SNR_muscle and SNR_liver (530 ± 120; 570 ± 110 vs. 370 ± 110; 400 ± 90; p < 0.001), improved diagnostic image quality by approximately 25%, and reduced respiratory artifacts by about 23%. Interobserver agreement was almost perfect. Importantly, the need for general anesthesia was significantly reduced using the 3D T1w VANE mDIXON (p < 0.001). Conclusions: Free-breathing 3D T1w VANE mDIXON chest MRI is a feasible and effective imaging approach for pediatric oncology patients, offering superior image quality and reducing the need for general anesthesia compared to conventional methods. Full article

(This article belongs to the Special Issue Pediatric Tumors: Diagnosis, Pathogenesis, Treatment, and Outcome)

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28 pages, 1088 KB

Open AccessArticle

Clinical and dGEMRIC Evaluation of Microfragmented Adipose Tissue Versus Hyaluronic Acid in Inflammatory Phenotype of Knee Osteoarthritis: A Randomized Controlled Trial

by Vilim Molnar, Željko Jeleč, Eduard Rod, Damir Hudetz, Petar Brlek, Igor Borić, Vid Matišić, Jana Mešić, Eduard Stjepan Pavelić, Dinko Vidović, Dejan Blažević, Fabijan Čukelj, Srećko Sabalić, Josip Štivičić, Tomislav Dujmović, Mario Starešinić, Martin Čemerin, David Glavaš Weinberger, Iva Molnar, Martina Smolić and Dragan Primorac Show full author list Hide full author list

Biomedicines 2025, 13(9), 2301; https://doi.org/10.3390/biomedicines13092301 - 19 Sep 2025

Viewed by 265

Abstract

Background: Knee osteoarthritis (OA) is a leading cause of disability, with limited therapies that modify both symptoms and structural degeneration. Autologous microfragmented adipose tissue (MFAT) has emerged as a promising regenerative option, especially in phenotypically distinct OA subgroups. This randomized controlled trial [...] Read more.

Background: Knee osteoarthritis (OA) is a leading cause of disability, with limited therapies that modify both symptoms and structural degeneration. Autologous microfragmented adipose tissue (MFAT) has emerged as a promising regenerative option, especially in phenotypically distinct OA subgroups. This randomized controlled trial evaluated the clinical and structural efficacy of intra-articular MFAT versus hyaluronic acid (HA) in patients with early to moderate inflammatory phenotype knee OA. Methods: Fifty-three patients were randomized in a 2:1 ratio to receive either MFAT (n = 35) or HA (n = 18). Patients were followed-up for six months post-injection and evaluated using patient-reported outcome measures (KOOS, WOMAC, VAS) and delayed gadolinium-enhanced MRI of cartilage (dGEMRIC). A responder analysis defined structural response as ≥10% increase in dGEMRIC in ≥3 of 7 predefined cartilage regions. Results: Both MFAT and HA led to statistically significant improvements in clinical scores and cartilage glycosaminoglycan content. MFAT showed greater mean improvements across most clinical and dGEMRIC measures, although without reaching statistical significance, except for KOOS Symptoms (MFAT: +25.0 vs. HA: +12.7, p = 0.008). Responder-level analysis revealed that all patients who demonstrated structural response also experienced clinically meaningful pain improvement (KOOS Pain ≥ 10), while no patient showed structural benefit without parallel symptomatic relief. Conclusions: MFAT led to greater improvement in symptoms related to joint stiffness, swelling, and crepitus compared to HA, reflecting its potential benefit in targeting the inflammatory features of knee OA. Importantly, HA also led to significant clinical and structural improvements, supporting its continued role as a standard-of-care comparator in knee OA management. Furthermore, the correlation between dGEMRIC and clinical response suggests its utility as a predictive biomarker of treatment success. Full article

(This article belongs to the Special Issue Osteoarthritis: Molecular Pathways and Novel Therapeutic Strategies—2nd Edition)

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16 pages, 1394 KB

Open AccessReview

A Potential Role of Adropin in Inflammatory Rheumatic Diseases—What Do We Know So Far?

by Petra Simac, Marin Petric, Marijana Jankovic Danolic and Dijana Perković

Biomedicines 2025, 13(9), 2300; https://doi.org/10.3390/biomedicines13092300 - 19 Sep 2025

Viewed by 187

Abstract

Adropin is a regulatory peptide hormone involved in metabolic homeostasis, cardiovascular protection, and immune modulation. Recent evidence suggests that adropin plays a role in the pathophysiology of autoimmune rheumatic diseases (ARDs) by influencing key processes such as endothelial function, oxidative stress, tissue fibrosis, [...] Read more.

Adropin is a regulatory peptide hormone involved in metabolic homeostasis, cardiovascular protection, and immune modulation. Recent evidence suggests that adropin plays a role in the pathophysiology of autoimmune rheumatic diseases (ARDs) by influencing key processes such as endothelial function, oxidative stress, tissue fibrosis, and immune cell regulation. This review summarizes current knowledge on adropin’s biological functions and its relevance in conditions including rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, primary Sjögren’s syndrome, osteoarthritis, psoriasis, Behçet’s disease, and Kawasaki disease. We discuss how adropin interacts with various signaling pathways and highlight its potential role in macrophage polarization, regulatory T cell activity, and fibrotic remodeling. Although data remain limited and sometimes conflicting, altered adropin levels have been observed across several ARDs, suggesting potential utility as a biomarker or therapeutic target. Further research is needed to clarify its clinical significance and translational potential in immune-mediated diseases. Full article

(This article belongs to the Section Immunology and Immunotherapy)

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28 pages, 3457 KB

Open AccessReview

Alveolar Epithelial Cell Dysfunction in Acute Respiratory Distress Syndrome: Mechanistic Insights and Targeted Interventions

by Jing Wang and Jie Chao

Biomedicines 2025, 13(9), 2299; https://doi.org/10.3390/biomedicines13092299 - 19 Sep 2025

Viewed by 135

Abstract

Acute respiratory distress syndrome (ARDS) is a life-threatening condition with high mortality. A central driver in its pathogenesis is alveolar epithelial cell (AEC) dysfunction, which leads to disruption of the epithelial barrier, impaired fluid clearance, and dysregulated inflammatory responses. This review summarizes the [...] Read more.

Acute respiratory distress syndrome (ARDS) is a life-threatening condition with high mortality. A central driver in its pathogenesis is alveolar epithelial cell (AEC) dysfunction, which leads to disruption of the epithelial barrier, impaired fluid clearance, and dysregulated inflammatory responses. This review summarizes the key mechanisms underlying AEC injury, including programmed cell death (apoptosis, pyroptosis, necroptosis, ferroptosis), oxidative stress, mitochondrial dysfunction, epigenetic reprogramming (DNA methylation, histone modifications), metabolic rewiring (succinate accumulation), and spatiotemporal heterogeneity revealed by single-cell sequencing and spatial transcriptomics. Multicellular crosstalk involving epithelial–immune–endothelial networks and the gut-lung axis further shapes disease progression. Building on these mechanistic foundations, we evaluate emerging AEC-targeted interventions such as pharmacologic agents (antioxidants, anti-inflammatories), biologics (mesenchymal stem cells and engineered exosomes), and gene-based approaches (adeno-associated virus and CRISPR-Cas9 systems delivered via smart nanocarriers). Complementary strategies include microbiome modulation through probiotics, short-chain fatty acids, or fecal microbiota transplantation, and biomarker-guided precision medicine (e.g., sRAGE, exosomal miRNAs) to enable promise individualized regimens. We also discuss translational hurdles, including nanotoxicity, mesenchymal stem cell (MSC) heterogeneity, and gene-editing safety, and highlight future opportunities involving AI-driven multi-omics, lung-on-chip platforms, and epithelium-centered regenerative therapies. By integrating mechanistic insights with innovative therapeutic strategies, this review aims to outline a roadmap toward epithelium-targeted, precision-guided therapies for ARDS. Full article

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

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16 pages, 297 KB

Open AccessReview

Adrenal Incidentaloma: From Silent Diagnosis to Clinical Challenge

by Alexandra Mirica, Dana-Mihaela Tilici, Diana Loreta Paun, Ana Maria Arnautu, Victor Nimigean and Sorin Paun

Biomedicines 2025, 13(9), 2298; https://doi.org/10.3390/biomedicines13092298 - 19 Sep 2025

Viewed by 220

Abstract

The widespread use of advanced imaging techniques has led to a rising incidence of adrenal incidentalomas (AIs), asymptomatic adrenal masses discovered during imaging for non-adrenal-related conditions. AIs represent a diagnostic and therapeutic challenge due to their varied etiology, secretory potential, and potential for [...] Read more.

The widespread use of advanced imaging techniques has led to a rising incidence of adrenal incidentalomas (AIs), asymptomatic adrenal masses discovered during imaging for non-adrenal-related conditions. AIs represent a diagnostic and therapeutic challenge due to their varied etiology, secretory potential, and potential for malignancy. This review aims to provide a comprehensive overview of the current knowledge on adrenal incidentalomas, focusing on their pathogenesis, diagnostic work-up, imaging features, hormonal evaluation, and evidence-based management, with a special emphasis on autonomous cortisol secretion (ACS). A thorough narrative review of the literature from the past two decades was conducted, synthesizing data from key international guidelines (ESE/ENSAT), observational studies, meta-analyses, and case series regarding the evaluation and treatment of AI. AI represents an increasingly relevant clinical condition requiring a multidisciplinary, personalized approach. Prompt endocrine and radiological evaluation is essential to identify hormonally active or potentially malignant tumors. The complexity of the natural history of AI and the evolving understanding of ACS underline the need for tailored follow-up and management strategies. Full article

(This article belongs to the Special Issue Advanced Cancer Diagnosis and Treatment: Third Edition)

11 pages, 837 KB

Open AccessArticle

Th2 Suppression Through Antigen Liver Expression Using mRNA-LNP Technology

by Kazunori Arai, Hanae Toyonaga, Lei Cheng and Hirotsugu Tanaka

Biomedicines 2025, 13(9), 2297; https://doi.org/10.3390/biomedicines13092297 - 19 Sep 2025

Viewed by 189

Abstract

Background: Messenger RNA-lipid nanoparticle (mRNA-LNP) is a cutting-edge nucleic acid intracellular delivery technology. Although the clinical use of the mRNA vaccine is being actively developed, the use of mRNA-LNP technology in common diseases such as allergies is still being investigated. The purpose of [...] Read more.

Background: Messenger RNA-lipid nanoparticle (mRNA-LNP) is a cutting-edge nucleic acid intracellular delivery technology. Although the clinical use of the mRNA vaccine is being actively developed, the use of mRNA-LNP technology in common diseases such as allergies is still being investigated. The purpose of this study is to test if immune response can be suppressed when an antigen is expressed in mice liver tissue with mRNA-LNP technology. Methods: We first designed mRNA which the ovalbumin (OVA) antigen expresses on the surface of the cells, and synthesized mRNA were encapsulated into LNP. This OVA-mRNA-LNP was evaluated with an OVA-sensitized mouse model. Splenocytes from OVA-sensitized mice were cultured with ex vivo OVA stimulation for Th2 cytokine production and Treg population analysis. Furthermore, OVA-mRNA-LNP was evaluated by both prophylactic and therapeutic administration in an OVA-induced mice airway inflammation model. Results: Th2 cytokines such as IL-4 and IL-5 were suppressed and the Treg population was increased in ex vivo OVA-stimulated splenocytes isolated from the OVA-mRNA-LNP administered group. Moreover, suppression of Th2 cytokines in Bronchoalveolar Lavage Fluid (BALF) from both the prophylactic and therapeutic OVA-mRNA-LNP administered cohort was observed (40–80% reduction in Th2 cytokines). Conclusions: The data suggests that mRNA-LNP technology, which is a safe, non-viral gene delivery system, can be an effective approach to suppress allergen-induced inflammation by expressing antigen in the liver tissue. Full article

(This article belongs to the Special Issue Advances in Novel Drug Discovery, Synthesis, and Evaluation)

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15 pages, 918 KB

Open AccessArticle

Iron Deficiency in Heart Failure: From ESC Guidelines to Clinical Practice at a Romanian Hospital

by Oana Sirbu, Andreea Tirnoveanu, Raluca Ecaterina Haliga, Victorita Sorodoc, Miruna Sava, Cristina Bologa, Ovidiu Rusalim Petris, Bianca Codrina Morarasu, Alexandra Diana Diaconu, Alexandr Ceasovschih, Catalina Lionte, Paula Cristina Morariu, Branco Adrian Morariu, Cristian Statescu, Radu Andy Sascau, Mariana Floria and Laurentiu Sorodoc

Biomedicines 2025, 13(9), 2296; https://doi.org/10.3390/biomedicines13092296 - 19 Sep 2025

Viewed by 183

Abstract

Background: Iron deficiency (ID) is a frequent comorbidity in heart failure (HF), associated with reduced functional capacity and poor prognosis. Although the European Society of Cardiology (ESC) guidelines recommend systematic screening and intravenous iron supplementation (IS), adherence in clinical practice remains limited. This [...] Read more.

Background: Iron deficiency (ID) is a frequent comorbidity in heart failure (HF), associated with reduced functional capacity and poor prognosis. Although the European Society of Cardiology (ESC) guidelines recommend systematic screening and intravenous iron supplementation (IS), adherence in clinical practice remains limited. This observational study aimed to evaluate how these recommendations are implemented into practice. Methods: We performed a retrospective study including 4348 patients hospitalized with HF (NYHA II-IV) in a tertiary internal medicine clinic in Eastern Europe between January 2018 and September 2022. Demographic data, comorbidities, laboratory parameters, echocardiographic findings were collected from electronic medical records. IS was defined as serum ferritin < 100 ng/mL. Results: Among HF patients, 2547 (58.7%) were screened for ID, and 1091 (42.8%) had absolute deficiency. Only 278 patients (25.5%) received intravenous ferric carbodymaltose. Treated patients were predominantly elderly (70.1% ≥ 70 years), female (60.4%), and often had ischemic or valvular disease. Patients receiving intravenous IS showed higher NT-proBNP and troponin levels. A progressive increase in IS use was observed during the study period, with a temporary decline during the COVID-19 pandemic. Conclusions: Despite relatively high screening rates, only one-quarter of HF patients with confirmed ID received intravenous IS. These findings highlight persistent gaps between guidelines and clinical practice, emphasizing the need for improved awareness and implementation of ESC recommendations to optimize outcomes in HF patients with ID. Full article

(This article belongs to the Special Issue Heart Failure: New Diagnostic and Therapeutic Approaches)

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18 pages, 940 KB

Open AccessArticle

Prognostic Significance of Venous-to-Arterial CO₂ Difference in Critically Ill Patients After Major Abdominal Surgery

by Gyeo Ra Lee and Eun Young Kim

Biomedicines 2025, 13(9), 2295; https://doi.org/10.3390/biomedicines13092295 - 18 Sep 2025

Viewed by 184

Abstract

Purpose: The venous-to-arterial carbon dioxide partial pressure difference [P(v-a)CO₂] reflects the adequacy of tissue perfusion, with elevated values suggesting impaired clearance of CO₂. While its prognostic role has been investigated in septic shock and high-risk surgery, evidence in postoperative [...] Read more.

Purpose: The venous-to-arterial carbon dioxide partial pressure difference [P(v-a)CO₂] reflects the adequacy of tissue perfusion, with elevated values suggesting impaired clearance of CO₂. While its prognostic role has been investigated in septic shock and high-risk surgery, evidence in postoperative critically ill patients remains limited. This study aimed to evaluate the prognostic value of ΔP(v-a)CO₂ after major abdominal surgery and its relationship with microcirculatory markers. Methods: We retrospectively analyzed 86 patients admitted to the intensive care unit (ICU) after major abdominal surgery between September 2020 and October 2023. Arterial and central venous blood gas analyses were performed immediately postoperatively and at 24 h. Patients were stratified into groups according to ΔP(v-a)CO₂ (≤ 0 vs. >0). Postoperative outcomes and correlations with central venous oxygen saturation (ScvO₂) were assessed. Results: In the subgroup analysis of patients with an initial P(v-a)CO₂ > 6 mmHg, those in the ΔP(v-a)CO₂ > 0 group required mechanical ventilation (54.5% vs. 22.2%, p = 0.033) and continuous renal replacement therapy (36.4% vs. 8.9%, p = 0.020) more frequently, with longer durations of both interventions (p = 0.011 and p = 0.016, respectively). ICU length of stay and the incidence of acute kidney injury were significantly lower in the ΔP(v-a)CO₂ ≤ 0 group. In addition, a modest negative correlation was observed between ScvO₂ measured at 24 h postoperatively and ΔP(v-a)CO₂. Conclusions: ΔP(v-a)CO₂ may serve as a useful marker for postoperative risk stratification in critically ill patients undergoing major abdominal surgery. However, given the retrospective design, small sample size, and single-center setting, these findings should be considered hypothesis-generating and require confirmation in larger, prospective multicenter studies. Full article

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

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16 pages, 798 KB

Open AccessReview

Tolerability and Shared Decision-Making in the Hormonal Management of Endometriosis-Associated Pain

by Diogo Pinto da Costa Viana, Leonardo Jacobsen, Igor Padovesi, Ana Comin, Eline Lobo de Souza Correia, Daniela Da Maia Fernandes and Ana Carolina Pires Dias

Biomedicines 2025, 13(9), 2294; https://doi.org/10.3390/biomedicines13092294 - 18 Sep 2025

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Abstract

Background: The management of endometriosis-associated pain has traditionally focused on analgesic efficacy. However, with high-level evidence demonstrating therapeutic equivalence among principal hormonal classes, the paradigm has shifted towards a patient-centred approach prioritising long-term tolerability and shared decision-making. Objectives: This review critically synthesises [...] Read more.

Background: The management of endometriosis-associated pain has traditionally focused on analgesic efficacy. However, with high-level evidence demonstrating therapeutic equivalence among principal hormonal classes, the paradigm has shifted towards a patient-centred approach prioritising long-term tolerability and shared decision-making. Objectives: This review critically synthesises the evidence for the three main hormonal therapies—gonadotropin-releasing hormone (GnRH) analogues, dienogest, and gestrinone—focusing on their distinct tolerability and safety profiles to inform this modern clinical framework. Methods: This narrative review followed the SANRA (Scale for the Assessment of Narrative Review Articles) guidelines. The literature search was performed in PubMed, Embase, and Web of Science in June 2025. Results: Our comparative analysis, based on a structured literature search adhering to SANRA guidelines, shows that while all three classes are effective, they present distinct benefit–risk profiles: GnRH analogues offer potent pain relief but induce a hypoestrogenic state requiring add-back therapy to mitigate bone loss and vasomotor symptoms; dienogest preserves bone mineral density but is associated with challenging bleeding patterns and potential mood disturbances; gestrinone provides robust efficacy with a favourable cardiovascular and skeletal safety profile, although its androgenic effects can significantly impact patient adherence. Conclusions: In the absence of a clear hierarchy of efficacy, the optimal therapeutic choice is not determined by potency, but by a collaborative process in which patient values and tolerance for specific adverse effects guide selection. This review provides a framework to facilitate this shared decision-making (SDM) in clinical practice. Full article

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

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5 pages, 181 KB

Open AccessEditorial

Editorial for the Special Issue: Recent Advances in Adipokines—2nd Edition

by Christa Buechler

Biomedicines 2025, 13(9), 2293; https://doi.org/10.3390/biomedicines13092293 - 18 Sep 2025

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Abstract

Adipokines are a steadily growing group of bioactive proteins that have mostly been studied in relation to obesity and obesity-associated metabolic diseases [...] Full article

(This article belongs to the Special Issue Recent Advances in Adipokines—2nd Edition)

16 pages, 404 KB

Open AccessArticle

Sex Differences in MASLD After Age 50: Presentation, Diagnosis, and Clinical Implications

by Ilaria Milani, Maria Eugenia Parrotta, Luca Colangeli, Marianna Chinucci, Simonetta Palleschi, Barbara Rossi, Paolo Sbraccia, Alessandro Mantovani, Frida Leonetti, Valeria Guglielmi and Danila Capoccia

Biomedicines 2025, 13(9), 2292; https://doi.org/10.3390/biomedicines13092292 - 18 Sep 2025

Viewed by 388

Abstract

Background: Age over 50, menopause, obesity and type 2 diabetes (T2D) are key risk factors for Metabolic dysfunction-associated steatotic liver disease (MASLD). This observational study aimed to assess sex differences in anthropometric and clinical profile, including non-invasive liver steatosis indices, in subjects [...] Read more.

Background: Age over 50, menopause, obesity and type 2 diabetes (T2D) are key risk factors for Metabolic dysfunction-associated steatotic liver disease (MASLD). This observational study aimed to assess sex differences in anthropometric and clinical profile, including non-invasive liver steatosis indices, in subjects with MASLD, obesity and/or T2D, aged ≥ 50 years. Methods: Anthropometric and clinical parameters, non-invasive indices for steatosis and fibrosis and FibroScan^® data were collected. Results: Among 213 patients (65.7% women, median age 63.0 years and mean Body Mass Index (BMI 34.9 kg/m²), men had higher body weight and waist circumference (WC), whereas women showed higher BMI and waist-to-height ratio (WHtR), and were more likely to exceed WC sex-specific and WHtR risk cut-offs. While transaminases values were higher in men, sex-specific cut-offs revealed that women more frequently exceeded these thresholds. No sex-differences were found for Fatty Liver Index (FLI), Fibrosis-4 (FIB-4) or FibroScan^®, although higher rate of mild fibrosis in women. The diagnostic accuracy of FLI for detecting steatosis was significantly higher in men and unsatisfactory in women (Area Under the ROC Curve, AUC 0.863 vs. 0.655). Conclusions: While MASLD is more common in men, these results suggest that postmenopausal women with visceral obesity showed similar or worse liver and cardiometabolic profiles than men, despite appearing healthier based on standard clinical parameters. Notably, common markers like transaminases and the FLI were less accurate in detecting steatosis in women, underscoring the need for sex-specific diagnostic criteria and greater clinical attention to older women, particularly those with central obesity, to ensure early identification and management of MASLD. Full article

(This article belongs to the Special Issue Connections Between Diabetes Mellitus, Other Metabolic and Endocrine Dysfunctions and Cardiovascular Pathologies—Second Edition)

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17 pages, 4717 KB

Open AccessArticle

Three-Dimensional Cartilage Tissue Engineering Using Placenta-Derived Extra-Embryonic Mesenchymal Stem Cells: From Isolation to Differentiation

by Cem Mujde and Atil Bisgin

Biomedicines 2025, 13(9), 2291; https://doi.org/10.3390/biomedicines13092291 - 18 Sep 2025

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Abstract

Background/Objectives: Mesenchymal stem cells (MSCs) offer promising prospects for novel treatment modalities in cellular therapies and artificial organ production. Despite a surge in artificial tissue research, there is a dearth of comprehensive studies detailing the entire process from stem cells to tissue [...] Read more.

Background/Objectives: Mesenchymal stem cells (MSCs) offer promising prospects for novel treatment modalities in cellular therapies and artificial organ production. Despite a surge in artificial tissue research, there is a dearth of comprehensive studies detailing the entire process from stem cells to tissue production, coupled with a scarcity. This study, however, presents the utility of extra-embryonic MSCs derived from placental tissue, traditionally considered as medical waste. Methods: Within a 3-dimensional cell culture system, histological assessments, and comprehensive optimization studies, the entire process required for artificial tissue production is addressed. Results: The results obtained are encouraging regarding the advancement of cellular therapies and artificial tissue engineering. However, challenges such as biopolymer degradation highlight the necessity for multistep approaches. Each analysis within this study delves into the discussion and optimization of key steps in artificial tissue production. Conclusions: Consequently, this study not only represents one of the first of its kind but also lays the groundwork for future investigations into relevant clinical applications. Full article

(This article belongs to the Special Issue Organoid, Organ-on-Chip and Advanced 2D/3D Models for Human Tissue Engineering Applications)

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17 pages, 723 KB

Open AccessReview

Rebuilding Mitochondrial Homeostasis and Inhibiting Ferroptosis: Therapeutic Mechanisms and Prospects for Spinal Cord Injury

by Qin Wang, Qingqing Qin, Wenqiang Liang, Haoran Guo, Yang Diao, Shengsheng Tian and Xin Wang

Biomedicines 2025, 13(9), 2290; https://doi.org/10.3390/biomedicines13092290 - 18 Sep 2025

Viewed by 240

Abstract

During the pathological process of spinal cord injury (SCI), ferroptosis is closely related to mitochondrial homeostasis. Following the occurrence of SCI, the interruption of local blood supply leads to mitochondrial damage within cells and a reduction in Adenosine triphosphate (ATP) production. This results [...] Read more.

During the pathological process of spinal cord injury (SCI), ferroptosis is closely related to mitochondrial homeostasis. Following the occurrence of SCI, the interruption of local blood supply leads to mitochondrial damage within cells and a reduction in Adenosine triphosphate (ATP) production. This results in the loss of transmembrane ion gradients, causing an influx of Ca²⁺ into the cells, which in turn generates a significant amount of Reactive oxygen species (ROS) and reactive nitrogen species. This leads to severe mitochondrial dysfunction and an imbalance in mitochondrial homeostasis. Ferroptosis is a form of programmed cell death that differs from other types of apoptosis, as it is dependent on the accumulation of iron and lipid peroxides, along with their byproducts. The double bond structures in intracellular polyunsaturated fatty acids (PUFA) are particularly susceptible to attack by ROS, leading to the formation of lipid alkyl free radicals. This accumulation of lipid peroxides within the cells triggers ferroptosis. After SCI, the triggering of ferroptosis is closely associated with the “death triangle”—a core network that catalyzes cell death through the interaction of three factors: local iron overload, collapse of antioxidant defenses, and dysregulation of PUFA metabolism (where PUFA are susceptible to attack by reactive ROS leading to lipid peroxidation). These three elements interact to form a central network driving cell death. In the pathological cascade of SCI, mitochondria serve as both a major source of ROS and a primary target of their attack, playing a crucial role in the initiation and execution of cellular ferroptosis. Mitochondrial homeostasis imbalance is not only a key inducer of the “death triangle” (such as the intensification of lipid peroxidation by mitochondrial ROS), but is also reverse-regulated by the “death triangle” (such as the destruction of mitochondrial structure by lipid peroxidation products). Through the cascade reaction of this triangular network, mitochondrial homeostasis imbalance and the “death triangle” jointly drive the progression of secondary damage. This study aims to synthesize the mechanisms by which various therapeutic approaches mitigate SCI through targeted regulation of mitochondrial homeostasis and inhibition of ferroptosis. Unlike previous research, we integrate the bidirectional regulatory relationship between “mitochondrial homeostasis disruption” and “ferroptosis” in SCI, and emphasize their importance as a synergistic therapeutic target. We not only elaborate in detail how mitochondrial homeostasis—including biogenesis, dynamics, and mitophagy—modulates the initiation and execution of ferroptosis, but also summarize recent strategies that simultaneously target both processes to achieve neuroprotection and functional recovery. Furthermore, this review highlights the translational potential of various treatments in blocking the pathological cascade driven by oxidative stress and lipid peroxidation. These insights provide a novel theoretical framework and propose combinatory therapeutic approaches, thereby laying the groundwork for designing precise and effective comprehensive treatment strategies for SCI in clinical settings. Full article

(This article belongs to the Special Issue Traumatic CNS Injury: From Bench to Bedside (2nd Edition))

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29 pages, 35177 KB

Open AccessArticle

Exploratory Analysis of Regulated Cell Death-Related Genes as Potential Prognostic Biomarkers in Endometrial Carcinoma

by Yu-Xuan Lin and Dong-Yan Cao

Biomedicines 2025, 13(9), 2289; https://doi.org/10.3390/biomedicines13092289 - 17 Sep 2025

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Abstract

Objective: This study aims to explore the mechanism of regulated cell death-related genes in the development of endometrial carcinoma. Methods: Endometrial carcinoma-related datasets were yielded via the Cancer Genome Atlas and Gene Expression Omnibus databases, and regulated cell death-related genes were extracted from [...] Read more.

Objective: This study aims to explore the mechanism of regulated cell death-related genes in the development of endometrial carcinoma. Methods: Endometrial carcinoma-related datasets were yielded via the Cancer Genome Atlas and Gene Expression Omnibus databases, and regulated cell death-related genes were extracted from the literature. Differential expression analysis, weighted gene co-expression network analysis, and protein interaction analysis were performed to identify critical regulated cell death-related genes. Gene set enrichment analysis was used to identify the functional pathways involved in these critical genes. Afterward, the best clustering approach for tumor samples was yielded via consensus clustering analysis, and nomogram prediction models were built. Shiny Methylation Analysis Resource Tool was used to compare the expression levels of CpG methylation probes for critical genes between tumor and normal samples. Spearman correlation analysis was conducted to investigate the relationship between critical genes and various immune features. Eventually, immuno-infiltrative analysis was implemented, and potential therapeutic agents were screened targeting critical genes. The data were analyzed and visualized by R software using different packages. In addition, the expressions of critical genes were validated by quantitative real-time polymerase chain reaction and immunochemistry. Results: Four critical genes, namely GBP2, SLC11A1, P2RX7, and HCLS1, were identified, and they were involved in various functional pathways such as leukocyte-mediated cytotoxicity. There were substantial differences in CpG methylation in GBP2, SLC11A1, and HCLS1 between tumor and normal samples. As for immune features, all critical genes were positively connected with immunosuppressive factors such as TIGIT and most HLA molecules in endometrial carcinoma. The critical genes high/low expression groups of tumor samples showed different immune responses towards PD-1, PD-L1, and CTLA-4 immunotherapy. The infiltration of 24 immune cells, such as effector memory CD8 T cells, was notably different between tumor and normal samples. Based on sensitivity analysis of chemotherapeutic agents, we found the highest positive correlation between SLC11A1 and “BI.2536” and the strongest passive correlation of HCLS1 and GBP2 with “Ribociclib”, as well as P2RX7 with “BMS.754807”. Quantitative real-time polymerase chain reaction suggested that the expression trends of GBP2, P2RX7, and HCLS1 were consistent with the results of bioinformatic analysis. Conclusions: Regulated cell death-related genes (GBP2, SLC11A1, P2RX7, and HCLS1) may play a role in endometrial carcinoma development, which can provide new ideas for the treatment and prognosis prediction of this disease. Full article

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

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Biomedicines, Volume 13, Issue 9 (September 2025) – 275 articles

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