Biomedicines

36 pages, 451 KiB

Open AccessReview

From Petri Dish to Primitive Heart: How IVF Alters Early Cardiac Gene Networks and Epigenetic Landscapes

by Charalampos Voros, Georgios Papadimas, Marianna Theodora, Despoina Mavrogianni, Diamantis Athanasiou, Ioakeim Sapantzoglou, Kyriakos Bananis, Antonia Athanasiou, Aikaterini Athanasiou, Charalampos Tsimpoukelis, Ioannis Papapanagiotou, Dimitrios Vaitsis, Aristotelis-Marios Koulakmanidis, Maria Anastasia Daskalaki, Vasileios Topalis, Nikolaos Thomakos, Panagiotis Antsaklis, Fotios Chatzinikolaou, Dimitrios Loutradis and Georgios Daskalakis

Biomedicines 2025, 13(8), 2044; https://doi.org/10.3390/biomedicines13082044 - 21 Aug 2025

Abstract

Numerous infants have been conceived by in vitro fertilization (IVF) and other assisted reproductive technologies (ART). Increasing evidence indicates that these approaches induce minor alterations in molecules during the initial phases of embryogenesis. This narrative review examines the molecular pathophysiology of embryonic cardiogenesis [...] Read more.

Numerous infants have been conceived by in vitro fertilization (IVF) and other assisted reproductive technologies (ART). Increasing evidence indicates that these approaches induce minor alterations in molecules during the initial phases of embryogenesis. This narrative review examines the molecular pathophysiology of embryonic cardiogenesis in the context of assisted reproductive technology, emphasizing transcriptional and epigenetic regulation. Essential transcription factors for cardiac development, including NKX2-5, GATA4, TBX5, ISL1, MEF2C, and HAND1/2, play a crucial role in mesodermal specification, heart tube formation, and chamber morphogenesis. Animal models and human preimplantation embryos have demonstrated that ART-related procedures, including gamete micromanipulation, supraphysiological hormone exposure, and extended in vitro culture, can alter the expression or epigenetic programming of these genes. Subsequent to ART, researchers have identified anomalous patterns of DNA methylation, alterations in histones, and modifications in chromatin accessibility in cardiogenic loci. These alterations indicate that errors occurred during the initial reprogramming process, potentially resulting in structural congenital heart abnormalities (CHDs) or modifications in cardiac function later in life. Analysis of the placental epigenome in babies conceived using assisted reproductive technology reveals that imprinted and developmental genes critical for cardiac development remain dysfunctional. This review proposes a mechanistic theory about the potential subtle alterations in the cardiogenic gene network induced by ART, synthesizing findings from molecular embryology, transcriptomics, and epigenomics. Understanding these molecular issues is crucial not only for enhancing ART protocols but also for evaluating the cardiovascular risk of children conceived by ART postnatally and for early intervention. Full article

(This article belongs to the Special Issue Epigenetic Regulation and Its Impact for Medicine (2nd Edition))

12 pages, 763 KiB

Open AccessArticle

Objective Biomarkers of Outdoor Activity (Vitamin D and CUVAF) in Young Adults with Myopia During and After the SARS-CoV-2 Pandemic

by Natali Gutierrez-Rodriguez, Miriam de la Puente-Carabot, Javier Andres Rodriguez-Hilarion, Jorge A. Ramos-Castaneda, Valentina Bilbao-Malavé, Carlos Javier Avendaño-Vasquez, Jorge Gonzalez-Zamora, Sandra Johanna Garzón-Parra and Sergio Recalde

Biomedicines 2025, 13(8), 2042; https://doi.org/10.3390/biomedicines13082042 - 21 Aug 2025

Abstract

Background/Objectives: Intrinsic biomarkers, such as serum vitamin D levels and the conjunctival ultraviolet autofluorescence (CUVAF) area, have been proposed to quantify sunlight exposure. Evidence suggests that reduced outdoor activity during the SARS-CoV-2 pandemic accelerated the progression of myopia; however, there is little [...] Read more.

Background/Objectives: Intrinsic biomarkers, such as serum vitamin D levels and the conjunctival ultraviolet autofluorescence (CUVAF) area, have been proposed to quantify sunlight exposure. Evidence suggests that reduced outdoor activity during the SARS-CoV-2 pandemic accelerated the progression of myopia; however, there is little information on the impact of such restrictions on vitamin D levels and CUVAF area in populations with myopia. This study aims to assess the association between serum vitamin D levels and conjunctival ultraviolet autofluorescence area (CUVAF) in young adults with myopia during and after the pandemic, as well as its relationship with sun exposure habits and the use of skin protection measures. Methods: A prospective observational study was carried out. A total of 59 students participated, 32 with a diagnosis of myopia and 27 controls, during SARS-CoV-2 pandemic. Two serological tests for total 25-hydroxy vitamin D (D2 + D3) (Calciferol) were taken, activity habits and sun exposure were identified using the Intermountain Live Well Institute tool, and CUVAF images were taken post-pandemic. Results: In the 59 participants, we observed similar vitamin D concentrations between the myopic and control groups during and after the pandemic. However, analysis of CUVAF areas after the pandemic revealed that myopes had significantly smaller areas compared to controls (p < 0.05). Conclusions: The study demonstrated that using vitamin D as a biomarker for outdoor activity requires additional investigation; the CUVAF biomarker showed a significant association with myopia. Full article

(This article belongs to the Topic Biomarkers of Disease: Discovery and Clinical Applications)

► Show Figures

Figure 1

14 pages, 5518 KiB

Open AccessArticle

NOD2 Promotes Glioblastoma Progression Through Effects on Epithelial–Mesenchymal Transition and Cancer Stemness

by Eshrat Jahan, Shubhash Chandra Chaudhary, S M Abdus Salam, Eun-Jung Ahn, Nah Ihm Kim, Tae-Young Jung, Jong-Hwan Park, Sung Sun Kim, Ji Young Lee, Kyung-Hwa Lee and Kyung-Sub Moon

Biomedicines 2025, 13(8), 2041; https://doi.org/10.3390/biomedicines13082041 - 21 Aug 2025

Abstract

Background: Glioblastoma multiforme (GBM) represents one of the most aggressive and lethal primary brain malignancies, characterized by rapid proliferation, extensive invasiveness, and a dismal prognosis. Emerging evidence implicates nucleotide-binding oligomerization domain-containing protein 2 (NOD2), an intracellular pattern recognition receptor, as [...] Read more.

Background: Glioblastoma multiforme (GBM) represents one of the most aggressive and lethal primary brain malignancies, characterized by rapid proliferation, extensive invasiveness, and a dismal prognosis. Emerging evidence implicates nucleotide-binding oligomerization domain-containing protein 2 (NOD2), an intracellular pattern recognition receptor, as a potential driver of GBM progression. This study investigates NOD2’s role in promoting glioblastoma through its effects on the epithelial–mesenchymal transition (EMT) and cancer stem cell (CSC) markers. Methods: NOD2 expression levels and survival outcomes were assessed using TCGA data from GBM tumor samples (n = 153) and normal brain tissues (n = 5). NOD2 protein expression was validated in glioma cell lines using Western blot and immunofluorescence analyses. Functional studies employed siRNA-mediated NOD2 knockdown to evaluate effects on cellular proliferation, migration, invasion, and colony formation, while correlations between NOD2 and EMT/CSC markers were assessed. Results: The analysis of TCGA data revealed a significantly elevated NOD2 expression in GBM tumors compared to normal brain tissue, with a high NOD2 expression correlating with a reduced disease-free survival in GBM patients. All tested glioma cell lines demonstrated robust NOD2 expression. Functional analyses demonstrated that NOD2 depletion substantially impaired cellular proliferation, migration, invasion, and the colony-forming capacity. Mechanistically, siRNA-mediated NOD2 knockdown significantly decreased the expression of EMT (Snail, SLUG, Vimentin) and CSC markers (CD44, CD133) at both protein and mRNA levels. Conclusions: Our results indicate that NOD2 contributes to GBM progression by influencing EMT and CSC pathways. These findings suggest NOD2’s potential as a therapeutic target in glioblastoma, highlighting the need for further mechanistic studies and therapeutic exploration. Full article

(This article belongs to the Special Issue Mechanisms and Novel Therapeutic Approaches for Gliomas)

► Show Figures

Figure 1

13 pages, 429 KiB

Open AccessArticle

ChOLE-Based Stratification of Cholesteatoma Surgery: Predictive Value for Recurrence and Hearing Recovery

by Yusuf Arslanhan, Ismail Aytac, Elif Baysal, Orhan Tunc, Berkay Guzel and Erhan Ciftel

Biomedicines 2025, 13(8), 2040; https://doi.org/10.3390/biomedicines13082040 - 21 Aug 2025

Abstract

Objectives: This study aimed to evaluate the clinical and hearing outcomes of patients with cholesteatomatous chronic otitis media using the ChOLE classification system and to assess its utility in predicting recurrence, guiding surgical approach, and anticipating hearing recovery. Materials and Methods: This retrospective [...] Read more.

Objectives: This study aimed to evaluate the clinical and hearing outcomes of patients with cholesteatomatous chronic otitis media using the ChOLE classification system and to assess its utility in predicting recurrence, guiding surgical approach, and anticipating hearing recovery. Materials and Methods: This retrospective study included 130 patients (141 ears) who underwent surgery for cholesteatoma between 2011 and 2020. Data were collected from surgical notes, imaging studies, and audiological evaluations. Patients were classified according to the ChOLE criteria, which incorporate cholesteatoma extension (Ch), ossicular chain status (O), and life-threatening complications (L). Surgical procedures and functional outcomes were compared across different stages and classification groups. Hearing outcomes were assessed in the early (3rd month) and late (2nd year) postoperative period. Results: Among the 130 patients (141 ears) evaluated, Stage II was the most common ChOLE stage (74.4%), followed by Stage I (17.7%) and Stage III (7.8%). The most frequently observed cholesteatoma extent was Ch3. A statistically significant association was found between surgical technique and ChOLE stage (p = 0.001): canal wall-down (CWD) tympanomastoidectomy was performed in 91% of Stage III cases and 84% of Stage II cases, whereas 76% of Stage I cases underwent canal wall-up (CWU) procedures. The overall recurrence rate was 29.5% in the CWU group and 16.4% in the CWD group, although this difference did not reach statistical significance (p = 0.792). However, ossicular chain status (O) showed a strong association with both early and late hearing outcomes. At 2 years, conductive hearing success was achieved in 90.9% of O0 patients, compared to 14% of O3b and 0% of O4 patients (p = 0.001). With regard to cholesteatoma extent (Ch), a statistically significant correlation was observed with early air–bone gap (ABG) closure success (p = 0.008) and late air conduction thresholds (p = 0.015). Similarly, ChOLE stage was significantly associated with early conductive hearing success (p = 0.012) and late ABG closure (p = 0.015). Overall, long-term hearing outcomes were superior to early results. Hearing success increased from 19.1% to 24.8% for air conduction thresholds and from 23% to 31.2% for hearing gain when comparing early and late follow-up periods. Conclusions: The ChOLE classification proved useful in guiding surgical strategy and predicting functional outcomes in cholesteatoma surgery. Advanced stage and greater cholesteatoma extension were associated with more extensive surgical procedures and poorer hearing results. Long-term audiological follow-up provided more accurate insights into surgical success. The standardized ChOLE system facilitates consistent reporting and meaningful comparison across institutions and studies. Full article

(This article belongs to the Special Issue Hearing Loss: Mechanisms and Targeted Interventions)

► Show Figures

Figure 1

24 pages, 726 KiB

Open AccessReview

Transcriptomic Comparisons of Somatic and Cancer Stem Cells

by Austin Drysch, Arun Ahuja, Dillan Prasad, Rishi Jain, Sharbel Romanos, Amr Alwakeal and Christopher Ahuja

Biomedicines 2025, 13(8), 2039; https://doi.org/10.3390/biomedicines13082039 - 21 Aug 2025

Abstract

Stem cells are essential for tissue maintenance, repair, and regeneration, yet their dysregulation gives rise to cancer stem cells (CSCs), which drive tumor progression, metastasis, and therapy resistance. Despite extensive research on stemness and oncogenesis, a critical gap remains in our understanding of [...] Read more.

Stem cells are essential for tissue maintenance, repair, and regeneration, yet their dysregulation gives rise to cancer stem cells (CSCs), which drive tumor progression, metastasis, and therapy resistance. Despite extensive research on stemness and oncogenesis, a critical gap remains in our understanding of how the transcriptomic landscapes of normal somatic stem cells (SSCs) diverge from those of CSCs to enable malignancy. This review synthesizes current knowledge of the key signaling pathways (Wnt, Notch, Hedgehog, TGF-β), transcription factors (Oct4, Sox2, Nanog, c-Myc, YAP/TAZ), and epigenetic mechanisms (chromatin remodeling, DNA methylation, microRNA regulation) that govern stemness in SSCs and are hijacked or dysregulated in CSCs. We highlight how context-specific modulation of these pathways distinguishes physiological regeneration from tumorigenesis. Importantly, we discuss the role of epithelial–mesenchymal transition (EMT), cellular plasticity, and microenvironmental cues in reprogramming and maintaining CSC phenotypes. By integrating transcriptomic and epigenetic insights across cancer biology and regenerative medicine, this review provides a framework for identifying vulnerabilities specific to CSCs while still preserving normal stem cell function. Understanding these distinctions is essential for the development of targeted therapies that minimize damage to healthy tissues and advance precision oncology. Full article

(This article belongs to the Special Issue Advances in Precision Cancer Therapy)

► Show Figures

Figure 1

18 pages, 310 KiB

Open AccessReview

Agnostic Biomarkers and Molecular Signatures in Colorectal Cancer—Guiding Chemotherapy and Predicting Response

by Ilektra Kyrochristou, Georgios D. Lianos, Gerasimia D. Kyrochristou, Georgios Anagnostopoulos, Christina Bali, Stergios Boussios, Michail Mitsis, Dimitrios Schizas and Konstantinos Vlachos

Biomedicines 2025, 13(8), 2038; https://doi.org/10.3390/biomedicines13082038 - 21 Aug 2025

Abstract

The concept of agnostic biomarkers—molecular modifications that guide therapy irrespective of tumor origin—has gained increasing relevance in oncology, including colorectal cancer (CRC). This review aims to critically evaluate the role of such biomarkers in CRC, highlighting their clinical significance as therapeutic targets and [...] Read more.

The concept of agnostic biomarkers—molecular modifications that guide therapy irrespective of tumor origin—has gained increasing relevance in oncology, including colorectal cancer (CRC). This review aims to critically evaluate the role of such biomarkers in CRC, highlighting their clinical significance as therapeutic targets and indicators of prognosis. Through a PubMed search using the terms “agnostic treatment AND colorectal cancer,” eight key studies were identified and qualitatively analyzed. We focus on several biomarkers commonly regarded as agnostic across tumor types, including BRAF V600E mutation, receptor tyrosine kinase (RTK) and PI3K fusions, the CpG island methylator phenotype (CIMP), high tumor mutational burden (TMB), and microsatellite instability (MSI). These markers are inspected for their prevalence in CRC, underlying pathophysiological mechanisms of cancer promotion, and predictive or prognostic implications. Moreover, we integrate findings from broader oncologic studies to contextualize the evolving role of agnostic biomarkers beyond organ-specific paradigms. Emerging evidence suggests that leveraging these molecular signatures may inform the use of targeted and immunotherapeutic agents as first-line options in select CRC populations. Collectively, agnostic biomarkers represent an auspicious avenue for personalizing CRC treatment, particularly in advanced-stage disease where traditional treatment options remain limited. Full article

(This article belongs to the Special Issue Advances in Liquid Biopsy from Technological Innovation to Therapeutic Intervention)

19 pages, 4023 KiB

Open AccessArticle

Ferroptosis as a Therapeutic Avenue in Triple-Negative Breast Cancer: Mechanistic Insights and Prognostic Potential

by Taimoor Riaz, Muhammad Ali Saleem, Muhammad Umar Muzafar Khan, Muhammad Abdul Rehman Rashid and Muhammad Zubair

Biomedicines 2025, 13(8), 2037; https://doi.org/10.3390/biomedicines13082037 - 21 Aug 2025

Abstract

Background and Aims: Triple-negative breast cancer (TNBC) is a clinically aggressive malignancy marked by rapid disease progression, limited therapeutic avenues, and high recurrence risk. Ferroptosis an iron-dependent, lipid peroxidation-driven form of regulated cell death that has emerged as a promising therapeutic vulnerability in [...] Read more.

Background and Aims: Triple-negative breast cancer (TNBC) is a clinically aggressive malignancy marked by rapid disease progression, limited therapeutic avenues, and high recurrence risk. Ferroptosis an iron-dependent, lipid peroxidation-driven form of regulated cell death that has emerged as a promising therapeutic vulnerability in oncology. This study delineates the ferroptosis-associated molecular architecture of TNBC to identify key regulatory genes with prognostic and translational significance. Methods: Transcriptomic profiles from the GSE103091 dataset (130 TNBC and 30 normal breast tissue samples) were analyzed to identify ferroptosis-related differentially expressed genes (DEGs) using GEO2R. Protein–protein interaction (PPI) networks were constructed via STRING and GeneMANIA, with functional enrichment performed through Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Reactome analyses. Prognostic relevance was evaluated using GEPIA, BC-GenExMiner, and Kaplan–Meier Plotter survival analyses. Results: Six ferroptosis drivers (MAPK1, TLR4, IFNG, ATM, ULK2, and ATF3) and five suppressors (NFS1, GCLC, TP63, CD44, and SRC) were identified alongside HMOX1, a bifunctional regulator with context-dependent pro- and anti-ferroptotic activity. Enrichment analyses revealed significant associations with oxidative stress regulation, autophagy, immune modulation, and tumor progression pathways. Elevated IFNG expression was consistently linked to improve overall, disease-free, and distant metastasis-free survival, underscoring its dual function in antitumor immunity and ferroptosis sensitization. Conclusions: Ferroptosis represents a critical axis in TNBC pathophysiology, with IFNG emerging as both a prognostic biomarker and a viable therapeutic target. These insights provide a mechanistic foundation for integrating ferroptosis-inducing agents with immunotherapeutic modalities to enhance clinical outcomes and overcome therapeutic resistance in TNBC. Full article

(This article belongs to the Special Issue Triple Negative Breast Cancer: From Mechanisms to Therapeutic Approaches)

► Show Figures

Figure 1

17 pages, 3553 KiB

Open AccessArticle

Comparative Evaluation of Computational Methods for Validating Housekeeping Gene RT-qPCR Data in 3T3-L1 Cells

by Zhenya Ivanova, Natalia Grigorova, Valeria Petrova, Ekaterina Vachkova and Georgi Beev

Biomedicines 2025, 13(8), 2036; https://doi.org/10.3390/biomedicines13082036 - 21 Aug 2025

Abstract

Background: Postbiotics with anti-adipogenic properties can significantly modify adipocyte metabolism by influencing key cellular pathways involved in lipid accumulation. In preliminary in vitro studies, it is essential to monitor various cellular and subcellular variables, including gene expression and protein synthesis potential, through RT-qPCR [...] Read more.

Background: Postbiotics with anti-adipogenic properties can significantly modify adipocyte metabolism by influencing key cellular pathways involved in lipid accumulation. In preliminary in vitro studies, it is essential to monitor various cellular and subcellular variables, including gene expression and protein synthesis potential, through RT-qPCR analysis. It is also crucial to select internal controls carefully and evaluate their stability for effective normalization and accurate interpretation of the results. Methods: In this study, we assessed the stability of six commonly used housekeeping genes: GAPDH, Actb, HPRT, HMBS, 18S, and 36B4. We analyzed their variability in mature 3T3-L1 adipocytes treated with supernatants from newly isolated Lacticaseibacillus paracasei strains. Our analysis combined classical statistical methods, a ∆Ct analysis, and software algorithms such as geNorm, NormFinder, BestKeeper, and RefFinder. Results: Our stepwise, multiparameter strategy for selecting reference genes led to the exclusion of Actb and 18S as the most variable reference genes. We identified HPRT as the most stable internal control. Additionally, HPRT and HMBS emerged as a stable pair, while the recommended triplet of genes for reliable normalization consists of HPRT, 36B4, and HMBS. Conclusions: The widely used putative genes in similar studies—GAPDH and Actb—did not confirm their presumed stability, which once again emphasizes the need for experimental validation of internal controls to increase the accuracy and reliability of gene expression. Combining a unique biological model—postbiotic-treated adipocytes—with multiple algorithms integrated into a single workflow allows us to provide a methodological template applicable to similar nutritional and metabolic research settings. Full article

(This article belongs to the Section Molecular Genetics and Genetic Diseases)

► Show Figures

Figure 1

14 pages, 14654 KiB

Open AccessArticle

Monitoring Beta-Blocker Therapy in Adolescents with Exercise-Induced Intraventricular Gradients Using Exercise Stress Echocardiography

by Nuno Cotrim, Hugo M. Café, Jorge Guardado, Pedro Cordeiro, Rui Martins, Hortense Cotrim and Carlos Cotrim

Biomedicines 2025, 13(8), 2035; https://doi.org/10.3390/biomedicines13082035 - 21 Aug 2025

Abstract

Background: Treadmill exercise stress echocardiography (ESE) is both feasible and safe in the pediatric population. Although regional wall motion abnormalities (RWMAs) have limited diagnostic utility, Doppler studies frequently demonstrate significant intraventricular pressure gradients (IVPGs) during exercise. These IVPGs, which were observed in 39% [...] Read more.

Background: Treadmill exercise stress echocardiography (ESE) is both feasible and safe in the pediatric population. Although regional wall motion abnormalities (RWMAs) have limited diagnostic utility, Doppler studies frequently demonstrate significant intraventricular pressure gradients (IVPGs) during exercise. These IVPGs, which were observed in 39% of 258 previously studied adolescents, are absent at rest. Their detection provides valuable insight into exercise-related symptoms and abnormal findings on resting or stress electrocardiograms (ECGs). Purpose: To evaluate the effect of β-blocker therapy on the occurrence of intraventricular pressure gradients (IVPGs) in adolescents presenting with symptoms or abnormal findings on resting or stress electrocardiograms (ECGs). Methods: Exercise stress echocardiography (ESE) was repeated in 66 of 101 adolescents who were found to have developed intraventricular pressure gradients (IVPGs) during the initial assessment. All participants had normal resting echocardiograms, and all underwent follow-up evaluation while receiving β-blocker therapy. The study cohort included 15 females (23%) and the mean age of participants was 14.6 ± 1.7 years (range: 11–17 years). Comprehensive two-dimensional and Doppler echocardiographic assessments were performed at baseline and during β-blocker treatment. Results: During the initial ESE, the mean intraventricular pressure gradient (IVPG) was 105 ± 38 mmHg. Under β-blocker therapy, 37 adolescents no longer developed IVPGs while, in the remaining 29 adolescents, the IVPG was significantly reduced to a mean of 58 ± 32 mmHg (p < 0.0001). The mean heart rate at peak exercise decreased from 178 ± 15 bpm at baseline to 157 ± 9 bpm during the repeat ESE under β-blocker treatment (p < 0.0001). Clinical symptoms were reproduced in forty-seven adolescents during the initial ESE, but occurred in only seven adolescents during treatment (p < 0.0001). Conclusions: In adolescents presenting with symptoms or abnormal resting or stress ECG findings, and exertional intraventricular pressure gradients (IVPGs), oral β-blocker therapy either prevented the occurrence of IVPGs or significantly reduced their severity. These hemodynamic improvements were associated with the resolution of clinical symptoms in 85% of the symptomatic cohort. Full article

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

► Show Figures

Figure 1

56 pages, 4337 KiB

Open AccessReview

Glycomics in Human Diseases and Its Emerging Role in Biomarker Discovery

by Sherifdeen Onigbinde, Moyinoluwa Adeniyi, Oluwatosin Daramola, Favour Chukwubueze, Md Mostofa Al Amin Bhuiyan, Judith Nwaiwu, Tuli Bhattacharjee and Yehia Mechref

Biomedicines 2025, 13(8), 2034; https://doi.org/10.3390/biomedicines13082034 - 21 Aug 2025

Abstract

Glycosylation, the enzymatic addition of glycans to proteins and lipids, is a critical post-translational modification that influences protein folding, stability, trafficking, immune modulation, and cell signaling. The vast structural diversity of glycans arising from differences in monosaccharide composition, branching, and terminal modifications such [...] Read more.

Glycosylation, the enzymatic addition of glycans to proteins and lipids, is a critical post-translational modification that influences protein folding, stability, trafficking, immune modulation, and cell signaling. The vast structural diversity of glycans arising from differences in monosaccharide composition, branching, and terminal modifications such as sialylation, fucosylation, and sulfation underpins their functional specificity and regulatory capacity. This review provides a comprehensive overview of glycan biosynthesis, with a focus on N-glycans, O-glycans, glycosaminoglycans (GAGs), and glycolipids. It explores their essential roles in maintaining cellular homeostasis, development, and immune surveillance. In health, glycans mediate cell–cell communication, protein interactions, and immune responses. In disease, however, aberrant glycosylation is increasingly recognized as a hallmark of numerous pathological conditions, including cancer, neurodegenerative disorders, autoimmune diseases, and a wide range of infectious diseases. Glycomic alterations contribute to tumor progression, immune evasion, therapy resistance, neuroinflammation, and synaptic dysfunction. Tumor-associated carbohydrate antigens (TACAs) and disease-specific glycoforms present novel opportunities for biomarker discovery and therapeutic targeting. Moreover, glycan-mediated host–pathogen interactions are central to microbial adhesion, immune escape, and virulence. This review highlights current advances in glycomics technologies, including mass spectrometry, lectin microarrays, and glycoengineering, which have enabled the high-resolution profiling of the glycome. It also highlights the emerging potential of single-cell glycomics and multi-omics integration in precision medicine. Understanding glycome and its dynamic regulation is essential for uncovering the molecular mechanisms of disease and translating glycomic insights into innovative diagnostic and therapeutic strategies. Full article

(This article belongs to the Special Issue Role of Glycomics in Health and Diseases)

► Show Figures

Figure 1

7 pages, 180 KiB

Open AccessBrief Report

Estimated Pulse Wave Velocity (ePWV) in Different Glaucoma Types

by Marija Bozic, Vesna Maric, Vladimir Milutinovic, Margita Lucic and Jelena Vasilijevic

Biomedicines 2025, 13(8), 2033; https://doi.org/10.3390/biomedicines13082033 - 21 Aug 2025

Abstract

Background/Objectives: This study aimed to evaluate estimated pulse wave velocity (ePWV) in different glaucoma types. Methods: This was observational, cross-sectional, non-interventional study conducted on 127 primary open-angle glaucoma (POAG) patients, 59 primary angle-closure glaucoma (PACG) patients, 34 pseudoexfoliative glaucoma (PEX) patients, [...] Read more.

Background/Objectives: This study aimed to evaluate estimated pulse wave velocity (ePWV) in different glaucoma types. Methods: This was observational, cross-sectional, non-interventional study conducted on 127 primary open-angle glaucoma (POAG) patients, 59 primary angle-closure glaucoma (PACG) patients, 34 pseudoexfoliative glaucoma (PEX) patients, and 55 normotensive glaucoma (NTG) patients (total of 275 glaucoma patients). The control group (CG, 92 patients) consisted of patients with cataract. ePWV was calculated by the formula that was recommended by the Reference Values for Arterial Stiffness Collaboration from data on age and mean arterial blood pressure. The obtained results were processed by applying methods of descriptive (arithmetical mean, standard deviation) and analytical statistics, and comparisons of tested variables were performed using ANOVA. A p value less than 0.05 was considered statistically significant. Results: Statistically significant differences were found between patients with POAG and the CG (p value 0.042), and between those with NTG and the CG (p value 0.001). There was a statistically significant difference in ePWV values when comparing all tested patients with glaucoma and the control group (p = 0.001). Conclusions: Estimated pulse wave velocity may be a helpful tool in future risk assessment models for glaucoma. Full article

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

15 pages, 24794 KiB

Open AccessArticle

CDK5RAP3 Deficiency Is Associated with Hepatic Inflammation and Increased Expression of NLRP3 Inflammasome Components

by Xinjin Chen, Yaqi Huang, Yilin Wu, Le Sheng, Hongchen Yan, Fanghui Chen, Fengwei Li, Hirpha Ketema and Yafei Cai

Biomedicines 2025, 13(8), 2030; https://doi.org/10.3390/biomedicines13082030 - 21 Aug 2025

Abstract

Background/Objectives: CDK5RAP3 (CDK5 regulatory subunit-associated protein 3), is a ubiquitously expressed protein in mammalian tissues, with emerging evidence suggesting its critical role in liver hypoplasia. CDK5RAP3 knockout results in liver hypoplasia and liver injury in mice, and most liver injuries are associated [...] Read more.

Background/Objectives: CDK5RAP3 (CDK5 regulatory subunit-associated protein 3), is a ubiquitously expressed protein in mammalian tissues, with emerging evidence suggesting its critical role in liver hypoplasia. CDK5RAP3 knockout results in liver hypoplasia and liver injury in mice, and most liver injuries are associated with inflammation. However, the connection between its deficiency and liver inflammation remains unclear. The NLRP3 inflammasome is a ubiquitously expressed inflammatory pathway, and growing evidence links it to liver diseases. Therefore, we aim to investigate the relationship between CDK5RAP3 deficiency in the liver and the NLRP3 inflammasome. Methods: To clarify the pathological link between CDK5RAP3 deficiency and liver inflammation, we developed liver-specific CDK5RAP3 knockout mouse models and mouse embryonic fibroblasts (MEFs) from conditional knockout mice. Results: CDK5RAP3 deficiency induces hepatic injury and inflammation in mice, with increased expression of NLRP3 inflammasome components (NLRP3, ASC, Caspase-1) and GSDMD, all of which promote pyroptosis. Notably, CDK5RAP3-deficient MEFs exhibit compromised proliferative capacity and elevated apoptotic rates. Conclusions: Our findings demonstrate that CDK5RAP3 is indispensable for maintaining hepatic homeostasis. Its deficiency can induce liver damage and inflammatory cell death in mice. Therefore, CDK5RAP3 may be a candidate for further investigation in inflammatory liver disease models. Full article

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

► Show Figures

Figure 1

12 pages, 269 KiB

Open AccessArticle

Chlamydia trachomatis-Specific Antibodies and In Vitro Fertilization Outcome

by Natasa Djordjevic, Ana Todorovic, Predrag Sazdanovic, Maja Sazdanovic, Marija Sorak, Aleksandra Gavrilovic, Aida Parandilovic, Eliana Garalejic, Marija Vujovic, Sanja Matic, Suzana Popović and Dejan Baskic

Biomedicines 2025, 13(8), 2032; https://doi.org/10.3390/biomedicines13082032 - 20 Aug 2025

Abstract

Objectives: Chlamydia trachomatis (CT) infection affects female fertility. The purpose of our study was to assess the association between serological and follicular fluid markers of CT infection and in vitro fertilization (IVF) success. Methods: This prospective multicenter cohort study included female [...] Read more.

Objectives: Chlamydia trachomatis (CT) infection affects female fertility. The purpose of our study was to assess the association between serological and follicular fluid markers of CT infection and in vitro fertilization (IVF) success. Methods: This prospective multicenter cohort study included female patients undergoing an IVF procedure in Serbia. The IVF procedure was performed according to the standard protocol. Serum and follicular fluid samples were collected during IVF, and anti-major outer membrane protein (anti-MOMP) IgG and IgA were determined by the Enzyme-Linked Immunosorbent Assay (ELISA) test. Results: A significantly higher embryo implantation rate was detected among patients negative for antibodies in follicular fluid (OR (95% CI): 5.254 (1.055; 26.152)). There was a trend toward increased risk of IVF failure in patients positive for either IgG or IgA in follicular fluid, or positive for IgG in serum. Older age was associated with lower odds for successful implantation (OR (95% CI): 0.888 (0.820; 0.962)), biochemical pregnancy (OR (95% CI): 0.890 (0.817; 0.969)), and live birth (OR (95% CI): 0.906 (0.833; 0.985)). Conclusions: Our results suggest that the presence of chlamydial anti-MOMP IgG and IgA in the serum and follicular fluid of infertile women could be indicative of lower IVF success rate, and that advanced maternal age is associated with higher risk of IVF failure. Full article

(This article belongs to the Special Issue The Art of ART (Assisted Reproductive Technologies))

26 pages, 2897 KiB

Open AccessArticle

Acceleration-Dependent Effects of Vibrotactile Gamma Stimulation on Cognitive Recovery and Cholinergic Function in a Scopolamine-Induced Neurotoxicity Mouse Model

by Tae-Woo Kim, Hee-Jung Park, Myeong-Hyun Nam, In-Ho Lee, Zu-Yu Chen, Hee-Deok Yun and Young-Kwon Seo

Biomedicines 2025, 13(8), 2031; https://doi.org/10.3390/biomedicines13082031 - 20 Aug 2025

Abstract

Background: Alzheimer’s disease is a progressive neurodegenerative disorder characterized by cognitive decline and memory loss. Gamma (γ) oscillations are closely linked to learning and memory, and recent interest has grown around Gamma ENtrainment Using Sensory stimulation (GENUS) as a non-invasive neuromodulation strategy. However, [...] Read more.

Background: Alzheimer’s disease is a progressive neurodegenerative disorder characterized by cognitive decline and memory loss. Gamma (γ) oscillations are closely linked to learning and memory, and recent interest has grown around Gamma ENtrainment Using Sensory stimulation (GENUS) as a non-invasive neuromodulation strategy. However, the therapeutic impact of vibrotactile gamma stimulation under varying physical parameters such as acceleration remains underexplored. Methods: Differentiated SH-SY5Y cells were treated with amyloid-β (Aβ) and exposed to vibrotactile stimulation at 2.2 or 4.0 m/s². In vivo, male C57BL/6N mice (7 weeks old, 35 g) were administered scopolamine to induce neurotoxicity and randomly assigned to sham, scopolamine, donepezil, or vibrotactile stimulation groups (n = 10 each). Behavioral tests, biochemical assays, Western blotting, and immunohistochemistry were performed to evaluate cognitive function, oxidative stress, cholinergic activity, synaptic plasticity, and neuroinflammation. Results: In vitro, SH-SY5Y cells exposed to amyloid-beta (Aβ) were treated with vibrotactile stimulation, resulting in enhanced neuronal marker expression at 2.2 m/s². In vivo, mice receiving stimulation at 2.2 m/s² showed improved cognitive performance, reduced oxidative stress, restored cholinergic function, suppressed neuroinflammation, and enhanced synaptic plasticity. Mechanistically, these effects were associated with activation of the AKT/GSK3β/β-catenin pathway. Conclusions: Our findings demonstrate that vibrotactile gamma stimulation at 2.2 m/s² exerts greater therapeutic efficacy than higher acceleration, highlighting the importance of optimizing stimulation parameters. This work supports the potential of acceleration-tuned, non-invasive GENUS-based therapies as effective strategies for cognitive recovery in neurodegenerative conditions. Full article

(This article belongs to the Special Issue Neurodegeneration No More: Cutting-Edge Technologies and Therapies in the Evolution of Neurodegenerative Disease Management—2nd Edition)

► Show Figures

Figure 1

10 pages, 236 KiB

Open AccessArticle

The Relationship Between Systemic Inflammatory Index and Other Inflammatory Markers with Clinical Severity of the Disease in Patients with Parkinson’s Disease

by Aybala Neslihan Alagoz, Aydan Dagdas, Sena Destan Bunul and Guldeniz Cetin Erci

Biomedicines 2025, 13(8), 2029; https://doi.org/10.3390/biomedicines13082029 - 20 Aug 2025

Abstract

Background/Objectives: Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra (SN), pathological accumulation of alpha-synuclein, and chronic neuroinflammation. The aim of this study is to evaluate the serum levels of systemic inflammatory [...] Read more.

Background/Objectives: Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra (SN), pathological accumulation of alpha-synuclein, and chronic neuroinflammation. The aim of this study is to evaluate the serum levels of systemic inflammatory markers such as neutrophil–lymphocyte ratio (NLR), neutrophil-HDL ratio (NHR), monocyte-HDL ratio (MHR), platelet–lymphocyte ratio (PLR), IL-6, IGF-1, systemic immune-inflammation index (SII), and systemic inflammation response index (SIRI) in patients with PD, and to analyze the relationship between these markers and the clinical stage of the disease as well as its motor and non-motor symptoms. Methods: Fifty-one patients diagnosed with PD and forty-nine HC matched for age and sex were evaluated prospectively. Results: NLR, NHR, and IGF-1 levels were found to be significantly higher in the PD group compared to the HC group (p < 0.05). There was no significant difference between the two groups in terms of PLR, MHR, SII, and SIRI. No significant relationship was found between the inflammatory markers and disease duration, clinical scales, or symptoms. Conclusions: These findings support the role of systemic inflammation in the pathophysiology of PD. Further multi-center, long-term follow-up studies—including simultaneous measurements of central nervous system inflammation markers—are needed for translation into clinical practice. Full article

(This article belongs to the Special Issue Neurodegenerative Diseases: From Mechanisms to Therapeutic Approaches, 2nd Edition)

21 pages, 4421 KiB

Open AccessSystematic Review

A Systematic Review of Clinical and Experimental Periodontitis Studies Demonstrating the Expression of PPAR-Gamma: A Meta-Analysis and Bioinformatics Approach

by Marco Antonio Rimachi Hidalgo, François Isnaldo Dias Caldeira, Silvana Regina Perez Orrico, Fabio Renato Manzolli Leite and Raquel Mantuaneli Scarel-Caminaga

Biomedicines 2025, 13(8), 2028; https://doi.org/10.3390/biomedicines13082028 - 20 Aug 2025

Abstract

Aim: Peroxisome Proliferator-Activated Receptor Gamma (PPAR-γ) plays important anti-inflammatory roles, including in periodontitis. This systematic review with a meta-analysis compiles evidence on the transcriptional and translational levels of PPAR-γ in clinical and experimental periodontitis studies, alongside functional enrichment and PPAR-γ interaction network analyses. [...] Read more.

Aim: Peroxisome Proliferator-Activated Receptor Gamma (PPAR-γ) plays important anti-inflammatory roles, including in periodontitis. This systematic review with a meta-analysis compiles evidence on the transcriptional and translational levels of PPAR-γ in clinical and experimental periodontitis studies, alongside functional enrichment and PPAR-γ interaction network analyses. Method: Electronic searches were conducted in six databases for publications up to February 2024. For the meta-analysis of experimental studies of periodontitis, PPAR-γ levels in the periodontal tissues were assessed through gene expression (RT-qPCR) or protein expression (Western blotting). In the clinical periodontitis studies, PPAR-γ levels in the gingival tissues were evaluated through protein expression (immunohistochemistry). A risk of bias (RoB) assessment was performed using the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE) and Newcastle Ottawa Scale (NOS) tools for experimental and clinical studies, respectively. The enrichment analysis was performed using the g:Profiler tool, and gene interaction networks were analyzed using GeneMANIA. Results: The meta-analysis demonstrated significantly lower PPAR-γ protein levels in the periodontal tissues from animals with periodontitis. PPARG mRNA and PPAR-γ quantification through immunohistochemistry remained inconclusive. The bioinformatics analyses indicated direct or indirect PPAR-γ-associated molecules involved in the immune response to periodontitis. The PPAR-γ protein expression was higher in periodontal tissues from healthy animals compared to that from those with periodontitis. Conclusions: Given the inconclusive findings of RT-qPCR and immunohistochemistry, further PPARG mRNA and PPAR-γ protein evaluations are needed to clarify their levels in the periodontal tissues. Full article

(This article belongs to the Special Issue Molecular Mechanisms and Therapeutic Approaches for Oral Disorders)

► Show Figures

Figure 1

21 pages, 2829 KiB

Open AccessSystematic Review

Comparative Safety of Anticoagulant, Antiplatelet and the Combination of Both for Acute Coronary Syndrome: A Systematic Review and Network Meta-Analysis

by Qingsheng Niu, Ziyi Zhu, Fulin Wang and Yaowen Jiang

Biomedicines 2025, 13(8), 2027; https://doi.org/10.3390/biomedicines13082027 - 20 Aug 2025

Abstract

Background: Antithrombotic therapy plays an important role in acute coronary syndrome (ACS). The combination of anticoagulant and antiplatelet therapy resulted in fewer complications and stronger potency compared to traditional monotherapy. Our net meta-analysis aimed to compare and rank the safety of different treatments [...] Read more.

Background: Antithrombotic therapy plays an important role in acute coronary syndrome (ACS). The combination of anticoagulant and antiplatelet therapy resulted in fewer complications and stronger potency compared to traditional monotherapy. Our net meta-analysis aimed to compare and rank the safety of different treatments used in patients with ACS. Method: We conducted a search for trials in three prominent databases. The main objective of our investigation was to assess hemorrhage. Additional outcomes included mortality, myocardial infarction, stroke, and embolism. We used a frequentist network meta-analysis with a random-effects model to, directly and indirectly, compare safety across different antithrombotic strategies. Result: A total of 30 randomized clinical trials were included in this net meta-analysis with 135,471 ACS patients. In these eight different antithrombotic therapies, SAPT (single-agent platelet inhibitor therapy) showed the lowest risk of bleeding (SUCRA = 0.5%). The highest risk of bleeding was observed in VKA (vitamin K antagonists) + DAPT (dual antiplatelet therapy) (SUCRA = 99.8%). Bleeding among NOAC (non-vitamin K antagonist oral anticoagulants) + DAPT was found to be higher than DAPT (OR = 1.94, 95% CI = 1.42–2.65). NOAC + SAPT significantly reduced the embolism (OR = 1.50, 95% CI = 1.16–1.94) and myocardial infarction (OR = 1.22, 95% CI = 1.08–1.37) events compared with SAPT. In addition, VKA significantly reduced the rate of stroke compared with SAPT (OR = 3.45, 95% CI = 1.17–10.18). However, no significant difference was observed in death events among these eight antithrombotic therapies. Conclusions: We advise against the use of SAPT in ACS due to its elevated risk of embolism, myocardial infarction, and stroke. It is important to mention that the combination of NOAC and SAPT has a lower incidence of myocardial infarction, bleeding and embolism problems. Therefore, the combination of NOAC and SAPT may be the optimal approach to achieve a balance between the risks of bleeding and embolism. This meta-analysis was registered in PROSPERO with the registration number CRD42024542826. Full article

(This article belongs to the Special Issue Coronary Artery Disease: From Pathophysiology to Therapeutic Strategies)

► Show Figures

Figure 1

20 pages, 1094 KiB

Open AccessArticle

Aims and Rationale of a National Registry Integrating Clinical, Echocardiographic, and Multi-Omics Profiling to Promote Precision Medicine in Peripartum Cardiomyopathy

by Alessia Palmentieri, Ciro Battaglia, Dario D’Alconzo, Luigi Anastasia, Luca Bardi, Giuseppe Bifulco, Maria Calanducci, Martina Carotenuto, Paolo Ivo Cavoretto, Federica Carusone, Emilio Di Lorenzo, MariaFrancesca Di Santo, Attilio Di Spiezio Sardo, Federica Ilardi, Danila Ioele, Francesca Lanni, Marco Licciardi, Francesco Loffredo, Rachele Manzo, Daniele Masarone, Nicolò Montali, Roberta Paolillo, Vanessa Peano, Giovanni Peretto, Enrica Pezzullo, Pina Polese, Gabriele Saccone, Alaide Chieffo, Giovanni Esposito and Cinzia Perrino Show full author list Hide full author list

Biomedicines 2025, 13(8), 2026; https://doi.org/10.3390/biomedicines13082026 - 20 Aug 2025

Abstract

Background. Peripartum cardiomyopathy (PPCM) is a rare but potentially life-threatening condition typically presenting as heart failure with reduced ejection fraction in the last month of pregnancy or in the first five months following delivery in women without other known causes of heart failure. [...] Read more.

Background. Peripartum cardiomyopathy (PPCM) is a rare but potentially life-threatening condition typically presenting as heart failure with reduced ejection fraction in the last month of pregnancy or in the first five months following delivery in women without other known causes of heart failure. PPCM incidence and prevalence are highly variable in different populations and geographical areas. The etiology of PPCM is likely multifactorial, with genetic predisposition, autoimmune conditions, nutritional deficiencies, hormonal and metabolic changes, myocardial inflammation, enhanced oxidative stress, vascular dysfunction, and angiogenic imbalance all listed as possible contributing factors. Objectives. The complexity and multifactorial nature of PPCM can be explored by large-scale “omics” investigations, and their integration has the potential to identify key drivers and pathways that have the largest contribution to the disease. The scarcity of relevant knowledge and experience with most rare diseases raises the unique need for cooperation and networking. Methods and results. In the context of PPCM, we hypothesize that the creation of prospective patient registries could represent an answer to this criticality. Therefore, we created a multicenter national registry of PPCM in different geographical areas in Italy. Conclusions. We expect that the integration of clinical, imaging and omics-based data might provide novel insights into PPCM pathophysiology and allow in the future early detection, risk assessment, and patient-specific therapeutic interventions, thereby offering new perspectives in precision medicine. Full article

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

► Show Figures

Graphical abstract

44 pages, 1023 KiB

Open AccessReview

Systemic Neurodegeneration and Brain Aging: Multi-Omics Disintegration, Proteostatic Collapse, and Network Failure Across the CNS

by Victor Voicu, Corneliu Toader, Matei Șerban, Răzvan-Adrian Covache-Busuioc and Alexandru Vlad Ciurea

Biomedicines 2025, 13(8), 2025; https://doi.org/10.3390/biomedicines13082025 - 20 Aug 2025

Abstract

Neurodegeneration is increasingly recognized not as a linear trajectory of protein accumulation, but as a multidimensional collapse of biological organization—spanning intracellular signaling, transcriptional identity, proteostatic integrity, organelle communication, and network-level computation. This review intends to synthesize emerging frameworks that reposition neurodegenerative diseases (ND) [...] Read more.

Neurodegeneration is increasingly recognized not as a linear trajectory of protein accumulation, but as a multidimensional collapse of biological organization—spanning intracellular signaling, transcriptional identity, proteostatic integrity, organelle communication, and network-level computation. This review intends to synthesize emerging frameworks that reposition neurodegenerative diseases (ND) as progressive breakdowns of interpretive cellular logic, rather than mere terminal consequences of protein aggregation or synaptic attrition. The discussion aims to provide a detailed mapping of how critical signaling pathways—including PI3K–AKT–mTOR, MAPK, Wnt/β-catenin, and integrated stress response cascades—undergo spatial and temporal disintegration. Special attention is directed toward the roles of RNA-binding proteins (e.g., TDP-43, FUS, ELAVL2), m6A epitranscriptomic modifiers (METTL3, YTHDF1, IGF2BP1), and non-canonical post-translational modifications (SUMOylation, crotonylation) in disrupting translation fidelity, proteostasis, and subcellular targeting. At the organelle level, the review seeks to highlight how the failure of ribosome-associated quality control (RQC), autophagosome–lysosome fusion machinery (STX17, SNAP29), and mitochondrial import/export systems (TIM/TOM complexes) generates cumulative stress and impairs neuronal triage. These dysfunctions are compounded by mitochondrial protease overload (LONP1, CLPP), UPR maladaptation, and phase-transitioned stress granules that sequester nucleocytoplasmic transport proteins and ribosomal subunits, especially in ALS and FTD contexts. Synaptic disassembly is treated not only as a downstream event, but as an early tipping point, driven by impaired PSD scaffolding, aberrant endosomal recycling (Rab5, Rab11), complement-mediated pruning (C1q/C3–CR3 axis), and excitatory–inhibitory imbalance linked to parvalbumin interneuron decay. Using insights from single-cell and spatial transcriptomics, the review illustrates how regional vulnerability to proteostatic and metabolic stress converges with signaling noise to produce entropic attractor collapse within core networks such as the DMN, SN, and FPCN. By framing neurodegeneration as an active loss of cellular and network “meaning-making”—a collapse of coordinated signal interpretation, triage prioritization, and adaptive response—the review aims to support a more integrative conceptual model. In this context, therapeutic direction may shift from damage containment toward restoring high-dimensional neuronal agency, via strategies that include the following elements: reprogrammable proteome-targeting agents (e.g., PROTACs), engineered autophagy adaptors, CRISPR-based BDNF enhancers, mitochondrial gatekeeping stabilizers, and glial-exosome neuroengineering. This synthesis intends to offer a translational scaffold for viewing neurodegeneration as not only a disorder of accumulation but as a systems-level failure of cellular reasoning—a perspective that may inform future efforts in resilience-based intervention and precision neurorestoration. Full article

(This article belongs to the Special Issue Cell Signaling and Molecular Regulation in Neurodegenerative Disease)

► Show Figures

Figure 1

12 pages, 275 KiB

Open AccessArticle

Factors Associated with Persistent Metatarsal Pain in Patients with Rheumatoid Arthritis in Remission: Clinical Implications and Multivariable Analysis in a Cross-Sectional Study

by Rebeca Bueno Fermoso, Maria Rosario Morales Lozano, Carmen Martínez Rincón, Pablo García-Fernández, Juan Miguel López González and Maria Luz González Fernandez

Biomedicines 2025, 13(8), 2024; https://doi.org/10.3390/biomedicines13082024 - 20 Aug 2025

Abstract

Background: Foot pain often persists in patients with rheumatoid arthritis (RA), even during clinical remission. However, its causes are not fully understood. Identifying factors specifically associated with metatarsal pain, rather than generalized foot pain, may improve targeted management strategies. Objectives: The [...] Read more.

Background: Foot pain often persists in patients with rheumatoid arthritis (RA), even during clinical remission. However, its causes are not fully understood. Identifying factors specifically associated with metatarsal pain, rather than generalized foot pain, may improve targeted management strategies. Objectives: The aim of this study was to compare the clinical, biomechanical, and radiological characteristics of RA patients in remission with isolated metatarsal pain versus those with pain in other foot regions, and to identify independent predictors of metatarsal pain. Methods: This cross-sectional study included 118 RA patients in remission, classified into two groups: isolated metatarsal pain (n = 61) and pain in other foot regions (n = 57). Clinical variables (demographics, disease duration, treatment, comorbidities), biomechanical measures (ankle, first metatarsophalangeal and subtalar joint mobility, hallux valgus severity, foot type), radiographic findings (erosions, subluxations), and ultrasound-detected synovitis in the 2nd–5th metatarsophalangeal (MTP) joints were recorded. Independent predictors were identified using binary logistic regression. Results: Patients with metatarsal pain had higher rates of severe hallux valgus, MTP synovitis, and dislocations ≥ 50%. Independent predictors were hallux valgus (OR = 5.428, 95% CI: 1.528–19.287, p = 0.009), MTP synovitis (OR = 2.093, 95% CI: 1.337–3.275, p = 0.001), and MTP dislocations (OR = 2.092, 95% CI: 1.275–3.432, p = 0.003). Conclusions: Persistent metatarsal pain in RA remission is associated with a distinct structural and biomechanical profile. Comparing foot pain by location may help identify clinically relevant patterns and support more individualized assessment and treatment strategies. Due to the cross-sectional design, causality cannot be established. Full article

(This article belongs to the Special Issue Pathogenesis, Diagnostics, and Therapeutics for Rheumatic Diseases)

13 pages, 876 KiB

Open AccessArticle

Machine Learning-Based Prediction of Short-Term Mortality After Coronary Artery Bypass Grafting: A Retrospective Cohort Study

by Islam Salikhanov, Volker Roth, Brigitta Gahl, Gregory Reid, Rosa Kolb, Daniel Dimanski, Bettina Kowol, Brian M. Mawad, Oliver Reuthebuch and Denis Berdajs

Biomedicines 2025, 13(8), 2023; https://doi.org/10.3390/biomedicines13082023 - 19 Aug 2025

Abstract

Objectives: This study aimed to develop and validate a machine learning (ML) algorithm to predict 30-day mortality following isolated coronary artery bypass grafting (CABG) and to compare its performance against the widely used European System for Cardiac Operative Risk Evaluation II (EuroSCORE II) [...] Read more.

Objectives: This study aimed to develop and validate a machine learning (ML) algorithm to predict 30-day mortality following isolated coronary artery bypass grafting (CABG) and to compare its performance against the widely used European System for Cardiac Operative Risk Evaluation II (EuroSCORE II) risk prediction model. Methods: In this retrospective study, we included consecutive adult patients who underwent isolated CABG between January 2009 and December 2022. Three predictive models were compared: (1) EuroSCORE II variables alone (baseline), (2) EuroSCORE II combined with additional preoperative variables (Model I), and (3) EuroSCORE II plus preoperative and postoperative variables available within five days after surgery (Model II). Logistic Regression (LR), Random Forest (RF), and Neural Network (NN) were employed and validated. Predictive accuracy was assessed using the area under the receiver operating characteristic curve (AUC) and specificity at 85% sensitivity. Results: Among the 3483 patients included, the mean age was 66.2 years (SD 10.3), with an overall 30-day mortality rate of 2.5%. The mean EuroSCORE II was 3.12 (SD 4.8). Integrating additional preoperative variables significantly improved specificity at 85% sensitivity for both random forest (from 42% to 51%; p < 0.001) and NN (from 28% to 43%; p < 0.001) but not for LR. Incorporating preoperative along with postoperative data (Model II) further improved specificity to approximately 70% across all ML methods (p < 0.001). The most influential postoperative predictors included kidney failure, pulmonary complications, and myocardial infarction. Conclusions: ML models incorporating preoperative and postoperative variables significantly outperform the traditional EuroSCORE II in predicting short-term mortality following isolated CABG. Full article

(This article belongs to the Special Issue Saving Lives from Myocardial Infarction: Prevention vs. Therapy)

27 pages, 1466 KiB

Open AccessReview

Curative Therapies for Hemophilias and Hemoglobinopathies in Adults: Immune, Gene, and Stem Cell Approaches in a Global Context

by Ayrton Bangolo, Behzad Amoozgar, Lili Zhang, Sarvarinder Gill, Daniel Lushimba Milolo, Justin Ngindu Kankonde, Claude Mbuyi Batakamuna, Robert Tassan, Christina Cho, John Bukasa-Kakamba and Kelley Mowatt-Pesce

Biomedicines 2025, 13(8), 2022; https://doi.org/10.3390/biomedicines13082022 - 19 Aug 2025

Abstract

Hemophilias and hemoglobinopathies—including hemophilias A and B, sickle cell disease (SCD), and β-thalassemia—are debilitating genetic disorders associated with significant global health burdens. While traditional management has centered on factor replacement and transfusions, these approaches remain palliative, with limited access and durability in many [...] Read more.

Hemophilias and hemoglobinopathies—including hemophilias A and B, sickle cell disease (SCD), and β-thalassemia—are debilitating genetic disorders associated with significant global health burdens. While traditional management has centered on factor replacement and transfusions, these approaches remain palliative, with limited access and durability in many regions. Recent advances in immune-based therapeutics (e.g., emicizumab, concizumab, crizanlizumab), viral vector-mediated gene addition (e.g., Roctavian, Hemgenix), and gene-modified autologous stem cell therapies (e.g., Zynteglo, Casgevy) have ushered in a new era of disease-modifying and potentially curative interventions. These therapies offer durable efficacy and improved quality of life, particularly in adult populations. However, implementation remains uneven across global health systems due to high costs, limited infrastructure, and regulatory heterogeneity. Additionally, ethical considerations such as long-term surveillance, informed consent in vulnerable populations, and social perceptions of genetic modification present ongoing challenges. Innovations such as multiplex genome editing, immune-evasive donor platforms, synthetic biology, and AI-driven treatment modeling are poised to expand therapeutic horizons. Equitable access, particularly in regions bearing the highest disease burden, will require collaborative funding strategies, regional capacity building, and inclusive regulatory frameworks. This review summarizes the current landscape of curative therapy, outlines implementation barriers, and calls for coordinated international action to ensure that transformative care reaches all affected individuals worldwide. Full article

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

► Show Figures

Figure 1

14 pages, 1089 KiB

Open AccessArticle

Vestibular Deficit in Patients with Waardenburg Syndrome

by Mathilde Benifla, Margaux Serey-Gaut, Emilie Bois, Salma Jbyeh, Natacha Teissier, Monique Elmaleh-Bergès, Laurence Jonard, Véronique Pingault, Natalie Loundon, Kahina Belhous, Sandrine Marlin and Audrey Maudoux

Biomedicines 2025, 13(8), 2021; https://doi.org/10.3390/biomedicines13082021 - 19 Aug 2025

Abstract

Background/Objectives: Waardenburg syndrome (WS) is a genetic disorder characterized by sensorineural hearing loss (SNHL) and pigmentation anomalies. While hearing impairment is a well-established feature of WS, vestibular dysfunction is also reported. This study aimed to investigate vestibular deficits in pediatric WS patients [...] Read more.

Background/Objectives: Waardenburg syndrome (WS) is a genetic disorder characterized by sensorineural hearing loss (SNHL) and pigmentation anomalies. While hearing impairment is a well-established feature of WS, vestibular dysfunction is also reported. This study aimed to investigate vestibular deficits in pediatric WS patients with SNHL, correlating these findings with molecular, audiometric, and radiological data to establish distinct phenotypic profiles for each WS subtype and associated pathogenic variants. Methods: This retrospective study included children with a genetically confirmed diagnosis of WS who underwent vestibular, auditory, and inner ear radiological assessments as part of their routine medical care between July 2000 and May 2022. Data were collected from medical records, including medical history, clinical findings, and assessment results. Results: Vestibular dysfunction was found to be highly prevalent, affecting 64% of the cohort, often impacting the canal sensory organ (89%) and occasionally the otolithic function (33%). Patients with SOX10 pathogenic variations exhibited a markedly higher risk of vestibular dysfunction, highlighting the unique role of SOX10 in inner ear development. Notably, inner ear malformations were identified in all SOX10-mutated subjects, whereas such anomalies were rare among individuals with other WS gene variants, occurring in only two additional cases with minor malformations. Conclusions: This study reveals a significant prevalence of vestibular deficits in pediatric WS patients with SNHL, emphasizing the need for routine vestibular assessments. The higher prevalence and severity of vestibular impairments in SOX10-mutated patients underscore the importance of molecular analysis in clinical diagnosis and management. Full article

(This article belongs to the Special Issue The Molecular Mechanisms of Hearing, Balance and Deafness)

► Show Figures

Figure 1

38 pages, 2700 KiB

Open AccessReview

From Microbial Switches to Metabolic Sensors: Rewiring the Gut–Brain Kynurenine Circuit

by Masaru Tanaka and László Vécsei

Biomedicines 2025, 13(8), 2020; https://doi.org/10.3390/biomedicines13082020 - 19 Aug 2025

Abstract

The kynurenine (KYN) metabolic pathway sits at the crossroads of immunity, metabolism, and neurobiology, yet its clinical translation remains fragmented. Emerging spatial omics, wearable chronobiology, and synthetic microbiota studies reveal that tryptophan (Trp) metabolism is regulated by distinct cellular “checkpoints” along the gut–brain [...] Read more.

The kynurenine (KYN) metabolic pathway sits at the crossroads of immunity, metabolism, and neurobiology, yet its clinical translation remains fragmented. Emerging spatial omics, wearable chronobiology, and synthetic microbiota studies reveal that tryptophan (Trp) metabolism is regulated by distinct cellular “checkpoints” along the gut–brain axis, finely modulated by sex differences, circadian rhythms, and microbiome composition. However, current interventions tackle single levers in isolation, leaving a key gap in the precision control of Trp’s fate. To address this, we drew upon an extensive body of the primary literature and databases, mapping enzyme expression across tissues at single-cell resolution and linking these profiles to clinical trials investigating dual indoleamine 2,3-dioxygenase 1 (IDO1)/tryptophan 2,3-dioxygenase (TDO) inhibitors, engineered probiotics, and chrono-modulated dosing strategies. We then developed decision-tree algorithms that rank therapeutic combinations against biomarker feedback loops derived from real-time saliva, plasma, and stool metabolomics. This synthesis pinpoints microglial and endothelial KYN hotspots, quantifies sex-specific chronotherapeutic windows, and identifies engineered Bifidobacterium consortia and dual inhibitors as synergistic nodes capable of reducing immunosuppressive KYN while preserving neuroprotective kynurenic acid. Here, we highlight a framework that couples lifestyle levers, bio-engineered microbes, and adaptive pharmaco-regimens into closed-loop “smart protocols.” By charting these intersections, this study offers a roadmap for biomarker-guided, multidisciplinary interventions that could recalibrate KYN metabolic activity across cancer, mood, neurodegeneration, and metabolic disorders, appealing to clinicians, bioengineers, and systems biologists alike. Full article

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

► Show Figures

Figure 1

36 pages, 19130 KiB

Open AccessArticle

The Transgenerational Impact of High-Fat Diet and Diabetic Pregnancy on Embryonic Transcriptomics and Mitochondrial Health

by Abigail K. Klein, Benjamin P. Derenge, Malini Mukherjee, Srikrishna P. Reddy, Tricia D. Larsen, Prathapan Ayyappan, Tyler C. T. Gandy, Kyle M. Siemers, Michael S. Kareta and Michelle L. Baack

Biomedicines 2025, 13(8), 2019; https://doi.org/10.3390/biomedicines13082019 - 19 Aug 2025

Abstract

Background/Objectives: Overnutrition increases comorbidities such as gestational diabetes during pregnancy that can have detrimental consequences for both parent and progeny. We previously reported that high-fat (HF) diet and late-gestation diabetes (DM) incite mitochondrial dysfunction, oxidative stress, and cardiometabolic disease in first generation (F1) [...] Read more.

Background/Objectives: Overnutrition increases comorbidities such as gestational diabetes during pregnancy that can have detrimental consequences for both parent and progeny. We previously reported that high-fat (HF) diet and late-gestation diabetes (DM) incite mitochondrial dysfunction, oxidative stress, and cardiometabolic disease in first generation (F1) rat offspring, partially through epigenomic and transcriptomic programming. Primordial germ cells, which become the second generation (F2), are also exposed, which could incite generational risk. This study aimed to determine whether the F2 transcriptome already has genomic variation at the preimplantation embryo stage, and whether variations normalize, persist or compound in the third generation (F3). Methods: F0 female rats were fed a control or HF diet, then DM was induced in HF-fed dams on gestational day (GD)14, exposing F1 offspring and F2 primordial germ cells to hyperlipidemia, hyperglycemia and fetal hyperinsulinemia during the last third of pregnancy. F1 pups were reared by healthy dams and bred to produce F2 embryos (F2e) and F2 pups. F2 offspring were bred to produce F3 embryos (F3e). Embryos were assessed by a novel grading method, live cell imaging, and single-cell RNA sequencing. Results: Embryo grades were not different, but HF+DM F2e had more cells while F3e had fewer cells and overall fewer embryos. HF+DM F2e had similar mitochondria quantity but a downregulation of genes involved in lipid metabolism and more oxidative stress, consistent with mitochondrial dysfunction. They also had an upregulation of chromatin-remodeling genes. The predicted developmental effect is accelerated embryo aging and epigenetic drift. In contrast, HF+DM F3e had an adaptive stress response leading to increased mitochondria quantity and an upregulation of genes involved in mitochondrial respiration, metabolism, and genomic repair that led to a predicted developmental effect of delayed embryo maturation. Conclusions: Although pathways vary, both generations have metabolically linked differentially expressed genes that influence cell fate and developmental pathways. In conclusion, HF+DM pregnancy can program the early embryonic transcriptome for three generations, despite an intergenerational healthy diet. Full article

(This article belongs to the Special Issue Central Role of Mitochondrial Oxidative Stress in the Pathophysiology of Disorders (2nd Edition))

► Show Figures

Figure 1

17 pages, 6478 KiB

Open AccessArticle

The Role of the ALDH Family in Predicting Prognosis and Therapy Response in Pancreatic Cancer

by Xing Wu, Bolin Zhang, Yijun Chen, Bogusz Trojanowicz, Yoshiaki Sunami and Jörg Kleeff

Biomedicines 2025, 13(8), 2018; https://doi.org/10.3390/biomedicines13082018 - 19 Aug 2025

Abstract

Background: Pancreatic cancer ranks as the fourth leading cause of cancer-related deaths in the USA. The human aldehyde dehydrogenase (ALDH) family comprises 19 functional members and has been implicated in prognosis and therapy resistance. However, it remains unclear which specific ALDHs are [...] Read more.

Background: Pancreatic cancer ranks as the fourth leading cause of cancer-related deaths in the USA. The human aldehyde dehydrogenase (ALDH) family comprises 19 functional members and has been implicated in prognosis and therapy resistance. However, it remains unclear which specific ALDHs are associated with adverse prognoses in pancreatic cancer. Methods: We obtained transcriptomic and clinical data for pancreatic adenocarcinoma (PAAD) from the TCGA, corresponding mutational data, and normal pancreatic tissue transcriptomic data from GTEx. Prognostic analysis was carried out using Kaplan–Meier analysis. KEGG and GO analyses were used for biological signaling pathways, and ESTIMATE algorithms were used for tumor microenvironment (TME) assessment. CIBERSORT algorithm, immune infiltration analysis, and OncoPredict algorithms were employed for predicting chemotherapy sensitivity. Results: Our study identified four of the 19 ALDH genes (ALDH1L1, ALDH3A1, ALDH3B1, ALDH5A1) that were significantly associated with pancreatic cancer prognosis. High expression of ALDH1L1, ALDH3A1, and ALDH3B1 was associated with shorter overall survival, while ALDH5A1 expression was associated with longer overall survival of pancreatic cancer patients. Clinicopathological analysis revealed a significant association with KRAS mutational status and ALDH3A1 expression. Immune correlation analysis indicated that high expression of ALDH3A1 and ALDH3B1 was associated with lower expression of CD8⁺ T cell-associated gene expression. ESTIMATE analyses further revealed that high expression of ALDH3A1 and ALDH3B1 was associated with lower levels of immune cell infiltration. PAAD tumors with low ALDH3A1 expression were more sensitive to paclitaxel. Immunohistochemical analysis demonstrated high expression of ALDH3A1 in pancreatic cancer cells of human tumor tissues compared to normal pancreatic tissues. Conclusions: This study unveils specific ALDH family members relevant for prognosis and chemotherapy response in pancreatic cancer patients. These findings contribute valuable insights into prognostic biomarkers and their potential clinical utility in the treatment of pancreatic adenocarcinoma. Full article

(This article belongs to the Special Issue Pancreatic Cancer: From Mechanisms to Therapeutic Approaches (3rd Edition))

► Show Figures

Figure 1

18 pages, 4041 KiB

Open AccessArticle

A Deep Learning Approach to Alzheimer’s Diagnosis Using EEG Data: Dual-Attention and Optuna-Optimized SVM

by Funda Bulut Arikan, Dilber Cetintas, Aziz Aksoy and Muhammed Yildirim

Biomedicines 2025, 13(8), 2017; https://doi.org/10.3390/biomedicines13082017 - 19 Aug 2025

Abstract

Background/Objectives: Alzheimer’s disease (AD) is a progressive neurodegenerative disorder, pathologically defined by the accumulation of amyloid-β plaques and tau-related neurofibrillary tangles in the brain. It represents a principal driver of cognitive deterioration in middle-aged and elderly populations. Early diagnosis and pharmacological management [...] Read more.

Background/Objectives: Alzheimer’s disease (AD) is a progressive neurodegenerative disorder, pathologically defined by the accumulation of amyloid-β plaques and tau-related neurofibrillary tangles in the brain. It represents a principal driver of cognitive deterioration in middle-aged and elderly populations. Early diagnosis and pharmacological management of the disease markedly improve both the quality and duration of life. Methods: Electroencephalography (EEG) is critical in detecting and analyzing Alzheimer’s disease. The widespread use of mobile EEG devices in recent years has necessitated real-time and effective data processing. However, extracting disease-specific features from EEG data still poses a significant challenge, especially in cases that must be completed quickly. This study aims to determine the frequency bands associated with Alzheimer’s disease in EEG data obtained from multiple channels and to accelerate the detection methods. An accurate classification that requires little computation is the primary goal. Results: EEG recordings of 48 individuals (24 AD and 24 healthy controls (HC)) obtained from Florida State University were divided into Alpha, Beta, Delta, Gamma, and Theta frequency bands; scalograms and spectrograms were generated for each frequency band. The effectiveness of these bands was evaluated using the MobileNetV2 architecture. The results showed that Delta and Beta frequency bands were the most significant for Alzheimer’s detection. By analyzing the features obtained from the Delta and Beta bands using the MobileNetV2 model integrated with the Dual-Attention Mechanism, it was determined that the attention mechanisms improved model performance by 2%. In addition, the use of an SVM classifier with hyperparameters optimized via Optuna resulted in approximately 3% performance improvement, suggesting that hyperparameter tuning may contribute positively to classification accuracy. Furthermore, combining features obtained from these frequency bands increased the detection performance when evaluated with larger datasets. Conclusions: The study demonstrates the potential of frequency band-based analyses and feature fusion methods to increase the accuracy and efficiency of Alzheimer’s diagnosis using EEG data. The results are promising; however, they should be interpreted with caution regarding their generalizability. Full article

(This article belongs to the Special Issue Neural Nexus: Interdisciplinary Perspectives on Neurological Disorders)

► Show Figures

Figure 1

17 pages, 2396 KiB

Open AccessReview

Early Non-Response to Neoadjuvant Chemotherapy Will Increase the Recurrence of Cervical Cancer: A Systematic Review

by Shiqing Huang, Runfeng Yang, Li Yang, Shiyi Kong and Kecheng Huang

Biomedicines 2025, 13(8), 2016; https://doi.org/10.3390/biomedicines13082016 - 19 Aug 2025

Viewed by 16

Abstract

Objectives: Cervical cancer remains a significant global health burden for women. While neoadjuvant chemotherapy (NACT) has emerged as a potential treatment option, the prognostic implications of early non-response to NACT remain inadequately characterized. This systematic review aims to elucidate the association between [...] Read more.

Objectives: Cervical cancer remains a significant global health burden for women. While neoadjuvant chemotherapy (NACT) has emerged as a potential treatment option, the prognostic implications of early non-response to NACT remain inadequately characterized. This systematic review aims to elucidate the association between early non-response to NACT and long-term disease-free survival (DFS) in cervical cancer patients. Methods: A comprehensive systematic review was conducted following PRISMA guidelines. PubMed, Embase, Elsevier, Springer, EBSCO, and Cochrane Library were systematically searched to identify eligible studies. Pooled hazard ratios (HRs) for DFS with 95% confidence intervals (CIs) were calculated using R software (version 4.5.1). Heterogeneity was assessed via Cochran’s Q test and I² statistics. Publication bias was evaluated using funnel plots, Begg’s test, Egger’s test, and trim-and-fill methods. Sensitivity analyses further validated result robustness. Results: Eleven studies (n = 2064 patients; 1546 responders, 518 non-responders) met inclusion criteria. The pooled early non-response rate ranged from 13% to 39%. Early non-response significantly correlated with poorer DFS (HR = 3.29, 95% CI 2.35–4.62). Subgroup analyses by response criteria showed HRs of 2.94 (95% CI 1.72–5.03) for WHO criteria and 4.00 (95% CI 2.52–6.34) for RECIST criteria. No significant publication bias was detected (Begg’s p = 0.35; Egger’s p = 0.28). Sensitivity analyses and trim-and-fill adjustments confirmed result stability. Conclusions: Early non-response to NACT predicts worse DFS in women with cervical cancer. These findings proposed the need for large-scale or prospective studies to validate the prognostic value of early non-response and optimize treatment strategies for non-responders. Future prospective trials with standardized protocols are essential to validate these findings and establish criteria for optimizing patient selection for NACT-based therapeutic strategies. Full article

(This article belongs to the Special Issue Current Perspectives on Gynecologic Cancers)

► Show Figures

Figure 1

11 pages, 4935 KiB

Open AccessArticle

Bullous Congenital Ichthyosiform Erythroderma with Tinea Capitis in Half-Siblings: Rare Phenomenon in Ichthyosis with Co-Existing Trichophyton rubrum Infection and Blocker Displacement Amplification for Mosaic Mutation Detection

by Jipeng Liu, Yujuan Fu, Qihao Zhang, Qi Chen, Yuxiang Yang, Yi Xue and Yunqing Ren

Biomedicines 2025, 13(8), 2015; https://doi.org/10.3390/biomedicines13082015 - 19 Aug 2025

Viewed by 99

Abstract

Background/Objectives: Bullous congenital ichthyosiform erythroderma (BCIE) is an inherited keratinization disorder caused by pathogenic variants in specific genes. Here, we report a pair of half-siblings with BCIE and tinea capitis due to Trichophyton rubrum (T. rubrum) and then review the [...] Read more.

Background/Objectives: Bullous congenital ichthyosiform erythroderma (BCIE) is an inherited keratinization disorder caused by pathogenic variants in specific genes. Here, we report a pair of half-siblings with BCIE and tinea capitis due to Trichophyton rubrum (T. rubrum) and then review the species of ichthyosis previously reported with T. rubrum infection. Methods: We performed dermatological examination, fungal culture, and genetic analysis using whole-exome sequencing (WES) and blocker displacement amplification (BDA)-based Sanger sequencing. Both patients received oral terbinafine once daily and topical bifonazole gel for tinea capitis. Results: The pair of half-siblings had exhibited generalized scaling and hyperkeratosis since birth. Both siblings subsequently developed scalp pustules and hair loss for several months. Genetic analysis identified a pathogenic variant in the keratin 10 (KRT10) gene, confirming BCIE diagnosis. Additionally, fungal culture revealed T. rubrum infection. The patients responded positively to oral terbinafine antifungal treatment. Conclusions: This case highlights the potential susceptibility of patients with BCIE to fungal infections, warranting clinical vigilance. Furthermore, it demonstrates the utility of the BDA-based mutation detection method for diagnosing BCIE, suggesting its promise for advancing personalized diagnosis and management in hereditary skin diseases. Full article

(This article belongs to the Special Issue Skin Diseases: From Molecular Mechanisms to Novel Therapeutic Approaches)

► Show Figures

Figure 1

25 pages, 1806 KiB

Open AccessReview

Beyond the Skin: Exploring the Gut–Skin Axis in Chronic Spontaneous Urticaria and Other Inflammatory Skin Diseases

by Laura Haidar, Camelia Felicia Bănărescu, Cristina Uța, Elena-Larisa Zimbru, Răzvan-Ionuț Zimbru, Alexandru Tîrziu, Raul Pătrașcu, Alina-Florina Șerb, Marius Georgescu, Daciana Nistor and Carmen Panaitescu

Biomedicines 2025, 13(8), 2014; https://doi.org/10.3390/biomedicines13082014 - 19 Aug 2025

Viewed by 178

Abstract

Emerging evidence suggests a critical role of the gut microbiome in modulating systemic immune responses, with increasing relevance in dermatological diseases. Chronic spontaneous urticaria (CSU), traditionally viewed as an isolated cutaneous disorder, is now recognized as a systemic immune condition involving complex interactions [...] Read more.

Emerging evidence suggests a critical role of the gut microbiome in modulating systemic immune responses, with increasing relevance in dermatological diseases. Chronic spontaneous urticaria (CSU), traditionally viewed as an isolated cutaneous disorder, is now recognized as a systemic immune condition involving complex interactions between innate and adaptive immunity, mast cell dysregulation, and non-IgE-mediated pathways. This review explores the gut–skin axis as a unifying concept linking intestinal dysbiosis to inflammatory skin diseases, including atopic dermatitis, psoriasis, rosacea, and acne. Special emphasis is placed on CSU, where altered gut microbial composition, characterized by reduced diversity, depletion of short-chain fatty acid-producing bacteria, and expansion of Proteobacteria, may contribute to increased intestinal permeability, systemic immune activation via toll-like receptors, and heightened mast cell sensitivity. We discuss findings from animal models demonstrating that gut microbiota modulation can attenuate mast cell hyperreactivity and reduce urticarial symptoms. In parallel, we examine clinical evidence supporting the potential role of probiotics, prebiotics, dietary interventions, and fecal microbiota transplantation as adjunctive strategies in CSU management. Despite promising findings, challenges remain in translating microbiome research into effective therapies due to interindividual variability, the complexity of host–microbiome interactions, and a lack of standardized protocols. Future research should focus on identifying predictive microbial patterns and developing personalized microbiome-targeted interventions. Understanding the bidirectional gut–skin relationship may open new therapeutic avenues beyond symptomatic treatment, positioning the microbiome as a novel target in CSU and related inflammatory dermatoses. Full article

(This article belongs to the Special Issue Urticaria: New Insights into Pathogenesis, Diagnosis and Therapy)

► Show Figures

Figure 1

Journal Menu

Journal Browser

Biomedicines, Volume 13, Issue 8 (August 2025) – 256 articles

Further Information

Guidelines

MDPI Initiatives

Follow MDPI