Biomedicines

37 pages, 2412 KB

Open AccessReview

Sympathetic Stress and Sleep Loss in Diabetic Retinopathy: Links to Retinal Blood-Flow Control

by Mengquan Tan, Shengtao Liu, Muxuan Fang, Man Yuan, Danping Niu, Yang Wang, Huixian Zhou, Jiling Zeng, Yaling Dai and Siyuan Song

Biomedicines 2026, 14(3), 736; https://doi.org/10.3390/biomedicines14030736 - 23 Mar 2026

Viewed by 1239

Abstract

Diabetic retinopathy (DR) is more than a capillary disorder. Diabetes affects neurons, glial cells, vascular cells, and immune signals within the retinal neurovascular unit (NVU). Retinal neurovascular coupling (NVC) is a useful functional marker of NVU integrity because it reflects the rise in [...] Read more.

Diabetic retinopathy (DR) is more than a capillary disorder. Diabetes affects neurons, glial cells, vascular cells, and immune signals within the retinal neurovascular unit (NVU). Retinal neurovascular coupling (NVC) is a useful functional marker of NVU integrity because it reflects the rise in local blood flow that follows neural activity. Many human flicker-light studies report smaller vessel dilation or weaker flow responses in diabetes. This finding can appear even in patients without clear fundus lesions. When NVC is reduced, retinal tissue may receive less oxygen. Lower oxygen delivery can raise oxidative stress and promote inflammation. These changes can then worsen vascular injury. This review describes key NVC pathways and diabetes-related NVU changes in Müller glia, astrocytes, microglia, pericytes, and endothelial cells. The review highlights sympathetic activation as a common stress signal. Pain, anxiety, perioperative stress, and sleep loss can increase sympathetic activity and circulating catecholamines. In the diabetic retina, vascular reserve is often limited. Under these conditions, catecholamines can increase mural cell constriction, reduce nitric oxide (NO)-dependent relaxation, and increase endothelial activation and barrier strain. These effects can shift the baseline state of glial and immune cells and further weaken NVC. The review also summarizes translational tools that can test these links. These tools include heart rate variability, standardized NVC protocols with diameter and flow measures, and retinal organoid and organ-on-a-chip platforms with controlled adrenergic exposure. The review discusses perioperative care packages that reduce stress responses, protect sleep, and manage glucose as practical ways to support retinal microcirculation. More longitudinal human studies are still needed. Retina-specific perioperative endpoints are also needed to clarify causality and to guide intervention trials. Full article

(This article belongs to the Special Issue Molecular Research on Diabetic Retinopathy (DR))

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17 pages, 1492 KB

Open AccessArticle

Antidepressant-Induced Apathy in Adolescents with a Depressive Episode While Taking Sertraline: Results of 8-Week Observational Study with Pharmacogenetic Testing for CYP2C19

by Dmitriy V. Ivashchenko, Sergey V. Grass, Vitaliy V. Sobur, Anna Y. Basova, Pavel V. Shimanov, Artem V. Shubin, Roman V. Deitch, Svetlana N. Tuchkova, Ivan N. Korsakov, Karin B. Mirzaev, Yuriy S. Shevchenko and Dmitry A. Sychev

Biomedicines 2026, 14(3), 735; https://doi.org/10.3390/biomedicines14030735 - 23 Mar 2026

Viewed by 1176

Abstract

Objectives. The aim of our study was to track changes in ODQ scores in adolescents with depressive episodes taking sertraline, depending on CYP2C19 polymorphisms. Methods. This study included 88 adolescents (88% were female) aged 12–17 who were prescribed sertraline. Emotional blunting [...] Read more.

Objectives. The aim of our study was to track changes in ODQ scores in adolescents with depressive episodes taking sertraline, depending on CYP2C19 polymorphisms. Methods. This study included 88 adolescents (88% were female) aged 12–17 who were prescribed sertraline. Emotional blunting was assessed using the Oxford Depression Questionnaire (ODQ) scale when the antidepressant was prescribed, after one, three, and 8 weeks, taking into account other medications used. Part 3 of the ODQ scale assessed the changes that occurred after the prescription of an antidepressant. All patients were genotyped for CYP2C19*2, *3, and *17. Based on genotypes, the phenotypes of the CYP2C19 isoenzyme were determined. Results. The ODQ score at the time of enrollment was higher (65[50;79] points) compared with after 8 weeks (38.5[32.5;56.5] points). Part 3 of the ODQ-26 questionnaire remained approximately the same for 8 weeks. Patients with higher ODQ-26 values at enrollment (73[56;83] vs. 59[44;71] points) were more likely to be prescribed antipsychotics. Differences in ODQ scores remained significant up to 3 weeks after enrollment (50.5[41.5;68] vs. 45.5[36;54] points). The comparison of ODQ scores and their dynamics did not show significant differences depending on CYP2C19*2 or *17 polymorphisms, or the type of CYP2C19 metabolism. Conclusions. There was no increase in emotional blunting according to the ODQ score among adolescents with depression who took sertraline for eight weeks. No significant correlations were found between the carrier status of CYP2C19 gene variants and the development of apathy induced by antidepressants. Full article

(This article belongs to the Special Issue Advanced Research on Psychiatric Disorders)

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24 pages, 2766 KB

Open AccessReview

Anti-Angiogenic Features of Endostatin in Obesity, Liver Fibrosis, and Hepatocellular Carcinoma

by Thomas Grewal and Christa Buechler

Biomedicines 2026, 14(3), 734; https://doi.org/10.3390/biomedicines14030734 - 23 Mar 2026

Viewed by 904

Abstract

Background/objectives: Endostatin is a cleavage product of collagen XVIII and a potent anti-angiogenic factor. Angiogenesis is essential for adipose tissue growth and contributes to liver fibrosis and cancer, suggesting a potential therapeutic role for endostatin in obesity, chronic liver diseases, and hepatocellular [...] Read more.

Background/objectives: Endostatin is a cleavage product of collagen XVIII and a potent anti-angiogenic factor. Angiogenesis is essential for adipose tissue growth and contributes to liver fibrosis and cancer, suggesting a potential therapeutic role for endostatin in obesity, chronic liver diseases, and hepatocellular carcinoma (HCC). This review article summarises published data on the role and expression of endostatin in obesity, liver injury, and HCC. Methods: PubMed and Google databases were searched using the terms “endostatin and liver”, “endostatin and HCC”, “endostatin and obesity”, and “endostatin and adipose”. Studies published in peer-reviewed journals relevant to this review were considered and reviewed for valuable insights. Results: Endostatin is much more than an inhibitor of angiogenesis; it exerts direct effects on adipocytes and myofibroblasts. Endostatin inhibits adipose tissue growth, and studies using Endostar—a modified form of endostatin approved in China for treating lung cancer—have demonstrated its protective effect in liver fibrosis. However, other studies have shown that endostatin activates hepatic stellate cells, indicating a role in tissue regeneration. Most research on endostatin has focused on cancer, and animal and human studies have shown the benefits of Endostar therapy in HCC. Conclusions: Endostar is a promising treatment for HCC and may also become an attractive drug for liver fibrosis. Hence, angiostatic therapy is not without risks and may only be suitable for selected patients. Full article

(This article belongs to the Special Issue Recent Advances in Adipokines (3nd Edition))

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16 pages, 10104 KB

Open AccessReview

En-Bloc Resection of Stage T4 Non-Small Cell Lung Cancer with Direct Spinal Invasion: Technical Considerations and Comprehensive Literature Review

by Wei-Ting Lee, Ke-Cheng Chen, Ching-Yao Yang, Yu-Cheng Yeh, Yen-Heng Lin, Yu-Cheng Huang, Jo-Yu Chen, Jin-Shing Chen and Fon-Yih Tsuang

Biomedicines 2026, 14(3), 733; https://doi.org/10.3390/biomedicines14030733 - 23 Mar 2026

Viewed by 812

Abstract

Historically, stage T4 non-small cell lung cancer (NSCLC) with direct spinal invasion was considered a definitive surgical contraindication due to the perceived inability to achieve negative margins without catastrophic morbidity. This paradigm has shifted through the advancement of specialized surgical techniques, which facilitate [...] Read more.

Historically, stage T4 non-small cell lung cancer (NSCLC) with direct spinal invasion was considered a definitive surgical contraindication due to the perceived inability to achieve negative margins without catastrophic morbidity. This paradigm has shifted through the advancement of specialized surgical techniques, which facilitate radical en-bloc resection in highly selected candidates by adhering to the en-bloc concept. This concept mandates the retrieval of the tumor and invaded vertebral segments as a single, contiguous unit to prevent intralesional transgression and local recurrence. Achieving microscopic negative margins (R0) stands as the most critical prognostic factor, as radical resection offers a significantly improved potential for long-term survival. Technical success requires a meticulously planned multidisciplinary approach encompassing varied surgical corridors—ranging from combined anterior–posterior windows to single-stage posterior-only approaches—tailored to the tumor’s anatomical level. Furthermore, preoperative hemostatic optimization using dual-energy computed tomography (DECT) for vascular assessment and transarterial embolization (TAE) has become indispensable for managing the hypervascularity of the invaded vertebral bone. This review synthesizes these evolving strategies, illustrated by a case of a 74-year-old male with stage T4 NSCLC where an R0 resection was achieved through a two-stage approach integrating uniportal video-assisted thoracoscopic surgery (VATS). Ultimately, en-bloc management provides a feasible and potential surgical strategy toward long-term survival for localized, spine-invasive lung cancer within a multidisciplinary treatment framework. Full article

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

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18 pages, 527 KB

Open AccessArticle

Do Serum Brain Biomarkers Differentiate the Hemorrhagic Head Injury Lesion Phenotypes? An Interim Analysis of an On-Going Randomized Clinical Trial

by Ayman El-Menyar, Naushad Ahmad Khan, Mohammad Asim, Husham Abdelrahman, Ammar Al-Hassani, Gustav Strandvik, Ashok Parchani, Ahmad Kloub, Sandro Rizoli and Hassan Al-Thani

Biomedicines 2026, 14(3), 732; https://doi.org/10.3390/biomedicines14030732 - 23 Mar 2026

Viewed by 836

Abstract

Background: Traumatic head injury (THI) includes a diverse range of hemorrhagic brain lesions (HBL), which are distinct phenotypes with characteristic pathophysiological mechanisms. Computed tomography (CT) is the cornerstone of the initial assessment and diagnosis; however, its sensitivity is limited, especially in mild [...] Read more.

Background: Traumatic head injury (THI) includes a diverse range of hemorrhagic brain lesions (HBL), which are distinct phenotypes with characteristic pathophysiological mechanisms. Computed tomography (CT) is the cornerstone of the initial assessment and diagnosis; however, its sensitivity is limited, especially in mild head injury. Blood-derived biomarkers, including Neuron-Specific Enolase (NSE) and S-100B, have been extensively studied; however, their efficacy in distinguishing HBL subtypes remains unclear. We evaluated whether circulating serum levels of S-100B and NSE can discriminate between distinct intracranial HBLs and extracranial hemorrhagic lesions (ECH). Methods: This is an interim analysis of a prospective, randomized, double-blind clinical trial including 434 adult patients with blunt THI. HBL phenotypes identified by CT scan included subarachnoid hemorrhage (SAH), subdural hematoma (SDH), epidural hematoma (EDH), and brain contusion (BC). Unique lesions were considered while overlapping lesions were excluded. Subgaleal hematoma (SGH) was included as an example of ECH. Serum S-100B was assessed within 6 h post-injury, while serum NSE was evaluated at admission, 24 h, and 48 h thereafter. Serum NSE and inflammatory cytokines were quantified in duplicates using a Human Magnetic Luminex 5-plex assay, while serum S-100B concentrations were measured separately. Serum epinephrine concentrations were quantified using an ELISA. Biomarker profiles were analyzed based on lesion phenotype, lesion multiplicity, injury pattern, and clinical outcomes, including hospital length of stay (HLOS) and the Glasgow Outcome Scale—Extended (GOSE). Results: Admission median S-100B levels were higher in patients with SAH (495 pg/mL) and lower in those with SGH (191 pg/mL); however, they did not show statistically significant difference among HBL phenotypes. They were significantly higher in patients with polytrauma TBI (420 pg/mL) compared to isolated TBI (258 pg/mL). Baseline and 48 h NSE concentrations were significantly higher in SDH (25,089 and 28,438 pg/mL) than in other THI lesions (p = 0.04). There were no statistically significant changes in NSE values over time across all THI lesions except for SDH in which they raised more after 48 h (p = 0.02). They had a significant drop in polytrauma over the time (p = 0.001). Compared to intracranial lesions, S-100 B levels were significantly lower in SGH and in skull fractures without intracranial hematomas. Both S-100B and NSE levels were elevated in individuals with unfavorable GOSE scores. Conclusions: In this secondary exploratory analysis, elevated serum NSE and S-100B levels discriminate between extra- and intracranial lesions and appear to represent distinct but complementary aspects of THI, indicating neuronal damage and its temporal evolution, and predicting clinical and functional outcomes. The present findings reflect association and not causation. Future studies incorporating larger or multicenter cohorts, volumetric imaging, and long-term outcomes are required to validate and refine biomarker-guided algorithms for personalized THI care. Full article

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

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13 pages, 479 KB

Open AccessArticle

Comparative Effects of Mineralocorticoid Receptor Antagonism on Organ Dysfunction in COVID-19-Associated ARDS

by Güleren Yartaş Dumanlı, Olcay Dilken, Oktay Demirkıran, Yalım Dikmen, Hafize Uzun and Omur Tabak

Biomedicines 2026, 14(3), 731; https://doi.org/10.3390/biomedicines14030731 - 23 Mar 2026

Viewed by 548

Abstract

Background/Objectives: Diuretics are recommended for hemodynamically stable patients with COVID-19-associated acute respiratory distress syndrome (ARDS) who have a positive fluid balance. However, furosemide use may be limited by hypokalemia in this population. We aimed to evaluate the clinical and biochemical effects of spironolactone [...] Read more.

Background/Objectives: Diuretics are recommended for hemodynamically stable patients with COVID-19-associated acute respiratory distress syndrome (ARDS) who have a positive fluid balance. However, furosemide use may be limited by hypokalemia in this population. We aimed to evaluate the clinical and biochemical effects of spironolactone in critically ill patients with COVID-19-associated ARDS. Methods: In this retrospective cohort study, 60 patients with COVID-19-associated ARDS admitted to the intensive care unit (ICU) between March and May 2020 were grouped according to diuretic therapy (furosemide vs. spironolactone). Patients were followed for five days (T0–T4). Demographic characteristics and clinical/laboratory parameters were recorded. A two-sided p value < 0.05 was considered statistically significant. Results: Thirty-one patients received furosemide (F group) and 29 received spironolactone (S group). On day 5, in the F group, cumulative fluid balance and serum sodium increased significantly over time (p < 0.05). Lactate increased significantly over time in both groups (p < 0.05). N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels increased significantly from T0 to T4 in the F group (p < 0.05). Conclusions: Spironolactone use was associated with a more favorable trajectory of organ dysfunction and improved volume, electrolyte, and cardiac stress marker dynamics compared with furosemide in patients with COVID-19-associated ARDS. Although confirmation in larger prospective studies is needed, spironolactone may be considered a reasonable diuretic alternative in selected patients, particularly when potassium preservation and avoidance of hypernatremia are clinical priorities. Full article

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

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4 pages, 170 KB

Open AccessEditorial

Network Biology and Translational Strategies in Liver Fibrosis

by Takefumi Kimura, Takanobu Iwadare and Shun-ichi Wakabayashi

Biomedicines 2026, 14(3), 730; https://doi.org/10.3390/biomedicines14030730 - 23 Mar 2026

Viewed by 539

Abstract

This Editorial introduces the Special Issue titled “Liver Fibrosis: Molecular Mechanisms, Potential Therapeutic Targets and Clinical Biomarkers” in Biomedicines [...] Full article

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

18 pages, 4860 KB

Open AccessArticle

Cumambrin B Alleviates Sepsis-Associated Acute Lung Injury by Activating the Nrf2/HO-1 Pathway

by Yuemei Que, Dandan Ruan, Minxia Xu, Ying Nie, Guozheng Huang, Huajun Zhao and Yanzi Yang

Biomedicines 2026, 14(3), 729; https://doi.org/10.3390/biomedicines14030729 - 23 Mar 2026

Viewed by 605

Abstract

Background: Sepsis-associated acute lung injury (SA-ALI) is a prevalent complication observed in patients with severe infection, characterized primarily by uncontrolled inflammatory response. Cumambrin B (CB) is a natural sesquiterpene lactone with anti-inflammatory properties. However, its protective effects against SA-ALI and the underlying molecular [...] Read more.

Background: Sepsis-associated acute lung injury (SA-ALI) is a prevalent complication observed in patients with severe infection, characterized primarily by uncontrolled inflammatory response. Cumambrin B (CB) is a natural sesquiterpene lactone with anti-inflammatory properties. However, its protective effects against SA-ALI and the underlying molecular mechanisms remain unclear. Methods: Mice that received intraperitoneal lipopolysaccharide (LPS) injection were used to assess the protective effect of CB on SA-ALI. LPS-induced RAW264.7 cells were utilized to delve into the molecular mechanisms responsible for its protective effects. Results: CB markedly alleviated lung tissue injury in mice with SA-ALI. Network pharmacology and combined in vitro and in vivo studies demonstrated that the protective effect of CB against SA-ALI was closely related to its anti-inflammatory and antioxidant activities. Meanwhile, CB restored mitochondrial function and activated the nuclear factor erythroid 2-related factor 2/heme oxygenase-1 (Nrf2/HO-1) signaling pathway. Furthermore, Nrf2 activator potentiated the inhibitory effects of CB on inflammation and oxidative stress, whereas these effects were abolished by an Nrf2 inhibitor. Conclusions: CB alleviates SA-ALI by restoring mitochondrial function, attenuating oxidative stress and inflammation via activation of the Nrf2/HO-1 pathway. Full article

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

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21 pages, 15778 KB

Open AccessArticle

Spatial Distribution of K13-Positive Airway Epithelial Cells in Idiopathic Pulmonary Fibrosis

by Fei Teng, Qi Zheng, Yansong Bai, Qianqian Zhao, Yanghe Fu, Huiqi Dai, Chenwen Huang and Tao Ren

Biomedicines 2026, 14(3), 728; https://doi.org/10.3390/biomedicines14030728 - 23 Mar 2026

Viewed by 786

Abstract

Background: The progression of idiopathic pulmonary fibrosis (IPF) involves distal airway remodeling and bronchiolization; however, the mechanisms driving these changes, particularly the contributions of epithelial stem cells, are not fully understood. K13⁺ hillock cells, normally quiescent in proximal airways, were examined [...] Read more.

Background: The progression of idiopathic pulmonary fibrosis (IPF) involves distal airway remodeling and bronchiolization; however, the mechanisms driving these changes, particularly the contributions of epithelial stem cells, are not fully understood. K13⁺ hillock cells, normally quiescent in proximal airways, were examined for their potential contribution to IPF pathogenesis. Methods: Spatial immunofluorescence was used to profile K13 expression along the airway axes in IPF and control lungs. Multiplex staining complemented by ex vivo culture assays was used to test expression stability. Single-cell RNA-sequencing (scRNA-seq) data were re-analyzed to identify cell subclusters and pathway enrichments. Meanwhile, cell–cell communication was inferred by using CellChat. Results: K13 was ectopically upregulated in IPF honeycomb cysts, triggering a proximal-like pseudostratified phenotype. This shift was marked by surges in K13⁺ regionally overlapping expression patterns (K5⁺, ~9%; CC10⁺, ~53%; ACE-TUB⁺, ~44%; MUC5AC⁺, ~23%) and a decline in SOX2 expression (~95% to ~64%), with ~70% of residual SOX2^low cells exhibiting elevated K13. Accompanying the expansion of K13⁺ subclusters (basal: 1.8% to 41.5%; club: 10.7% to 31.5%), it was observed that the profibrotic markers (K17, S100A2, LGALS7, IGFBP6) and ontologies related to RNA processing, stress response, and senescence were also enriched. These subclusters also amplified pro-fibrotic signaling (e.g., TGF-β, SEMA3, and GALECTIN-9) associated with epithelial subtypes and HAS1^high fibroblasts. Conclusions: Here, we demonstrate that K13⁺ cell activation is a pivotal event, driving the dysregulated proximalization of distal airways in IPF through fate reprogramming and epithelial-mesenchymal crosstalk. Thus, elucidating these K13-mediated fate dynamics provides a critical framework for understanding IPF pathogenesis. Full article

(This article belongs to the Special Issue Advanced Research in Pulmonary Pathophysiology)

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21 pages, 13801 KB

Open AccessArticle

Human Umbilical Cord Mesenchymal Stem Cells Protect Against Steroid-Induced Osteonecrosis of the Femoral Head Through Hippo Pathway

by Hengte Xing, Wenxiang Cai, Junwen Chen, Hanzhe Xu, Yubiao Zhang, Changheng Zhong, Jianlin Zhou and Hao Peng

Biomedicines 2026, 14(3), 727; https://doi.org/10.3390/biomedicines14030727 - 22 Mar 2026

Viewed by 881

Abstract

Background: Glucocorticoids (GCs) are a key pathogenic factor in steroid-induced avascular necrosis of the femoral head (SANFH). GCs can directly damage bone microvascular endothelial cells (BMECs), leading to impaired intraosseous blood supply. Recent studies suggest the Hippo signaling pathway may be involved in [...] Read more.

Background: Glucocorticoids (GCs) are a key pathogenic factor in steroid-induced avascular necrosis of the femoral head (SANFH). GCs can directly damage bone microvascular endothelial cells (BMECs), leading to impaired intraosseous blood supply. Recent studies suggest the Hippo signaling pathway may be involved in the pathogenesis of SANFH; however, its role in vascular endothelial repair and angiogenesis remains unclear. This study aims to investigate the therapeutic effects of human umbilical cord mesenchymal stem cells (hUC-MSCs) on SANFH, with a particular focus on their protective or reparative mechanisms on BMECs. Methods: In vivo, a SANFH mouse model is established and divided into NC, MPS, and hUC-MSCs groups, followed by Micro-CT imagin, hematoxylin and eosin (HE) staining and immunohistochemistry (IHC) (n = 8 per group). In vitro, BMECs are divided into NC, dexamethasone (Dex), hUC-MSCs, and Fer-1 groups to analyze cellular biological behaviors. Target protein expression is assessed using Western blotting and immunofluorescence microscopy. Ferroptosis-related markers are detected via biochemical assays. Mitochondrial ultrastructural changes are observed using transmission electron microscopy. Results: In vivo, the MPS group exhibited significant bone cavitation, sparse trabeculae, and disrupted trabecular architecture in the femoral head. The hUC-MSCs group showed marked improvement in bone microstructure, HE staining showed a significant decrease in the empty lacunae rate in the femoral head, and IHC results revealed markedly increased expression of cluster of differentiation 31 (CD31) and vascular endothelial growth factor (VEGF). In vitro, Dex stimulation suppressed BMECs proliferation. In Dex-treated cells, levels of intracellular reactive oxygen species (ROS), lipid peroxides, ferrous ion (Fe²⁺), malondialdehyde (MDA), acyl-CoA synthetase long chain family member 4 (ACSL4) and nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) were all increased, while expression of glutathione (GSH) and glutathione Peroxidase 4 (GPX4) was reduced. Transmission electron microscopy revealed plasma membrane rupture and reduction or loss of mitochondrial cristae. Furthermore, Dex promoted Hippo-mediated phosphorylation of Yes-associated protein (YAP)/Transcriptional coactivator with PDZ-binding motif (TAZ), upregulated NOX4 expression, and suppressed CD31 and VEGF expression. Following hUC-MSCs treatment, BMECs demonstrated enhanced proliferation, migration, and tube-forming capacity. Cellular GSH and GPX4 levels increased, antioxidant capacity was restored, peroxide accumulation decreased, and cells were protected from ferroptosis-effects comparable to those in the Fer-1 group. Additionally, hUC-MSCs inhibited YAP/TAZ phosphorylation and promoted elevated expression of CD31 and VEGF. Conclusions: These findings suggest that hUC-MSCs may attenuate Dex-induced ferroptosis in BMECs, enhance BMEC migration and angiogenesis, and improve femoral head microstructure in SANFH through modulation of the Hippo-YAP/TAZ signaling pathway. This study provides novel insights into the therapeutic potential of hUC-MSCs for SANFH. Full article

(This article belongs to the Special Issue New Insights into Bone and Cartilage Biology (2nd Edition))

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13 pages, 2133 KB

Open AccessReview

Targeted Interference with USF2 Binding to the SERPINE1 Proximal Promoter E-Box in Dual Mutant p53^R282Q,H179Y Human Keratinocytes Inhibits Serum-/TGF-β1-Induced SERPINE1 Expression and Stimulates Epithelial Cell Proliferation

by Stephen P. Higgins, Ralf-Peter Czekay, Craig E. Higgins and Paul J. Higgins

Biomedicines 2026, 14(3), 726; https://doi.org/10.3390/biomedicines14030726 - 22 Mar 2026

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Abstract

The SERPINE1 gene encodes the serine protease inhibitor plasminogen activator inhibitor type-1 (PAI-1), a major negative regulator of the plasmin-dependent pericellular proteolytic cascade and a crucial determinant in the program of stromal remodeling. Recent omics approaches confirmed that high tumor SERPINE1 levels are [...] Read more.

The SERPINE1 gene encodes the serine protease inhibitor plasminogen activator inhibitor type-1 (PAI-1), a major negative regulator of the plasmin-dependent pericellular proteolytic cascade and a crucial determinant in the program of stromal remodeling. Recent omics approaches confirmed that high tumor SERPINE1 levels are prognostic for poor disease outcomes and shorter disease-free survival in various malignancies. Kinetic analysis of biomarkers of cell cycle transit in growth-synchronized p53 dual mutant human keratinocytes confirmed that PAI-1 transcription occurred early after growth activation of quiescent (G₀) cells and prior to G1 entry. Previous evidence has confirmed that differential residence of USF family members (USF1→USF2 switch) at the PE2 region hexanucleotide E box motif (CACGTG) in the SERPINE1 proximal promoter characterizes the G₀→G₁ transition period and the transcriptional status of the SERPINE1 gene. A consensus PE2 E box motif (5′-CACGTG-3′) at nucleotides −566 to −561 is required for USF occupancy of the PE2 E box and serum-stimulated SERPINE1 transcription. Interference with USF2 occupancy of the PE2 E Box site by a double-stranded PE2 “decoy”, or induced expression of a dominant-negative USF (A-USF) construct, attenuate serum- and TGF-β1-stimulated SERPINE1 synthesis. Tet-Off activation of an A-USF insert reduced both PAI-1 and PAI-2 transcripts while increasing the fraction of proliferating (Ki-67⁺ cells). Conversely, overexpression of USF2 or adenoviral delivery of a PAI-1 vector inhibited HaCaT colony expansion. These findings are discussed in this review and collectively suggest that the USF1→USF2 transition at the PE2 E box site and subsequent SERPINE1 transcription impact serum-stimulated keratinocyte growth and, likely, cell cycle progression. Full article

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

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11 pages, 374 KB

Open AccessArticle

Medication Adherence and Risks of Mortality and End-Organ Damage in Asian Patients with Type 2 Diabetes: A Cohort Study from Southern Taiwan

by Peng-Wen Chen, Ming-Chieh Lin, Tzu-Jung Fang and Mei-Yueh Lee

Biomedicines 2026, 14(3), 725; https://doi.org/10.3390/biomedicines14030725 - 22 Mar 2026

Viewed by 533

Abstract

Background: Medication adherence is a critical component of effective management in type 2 diabetes mellitus (T2DM). Although previous studies have explored the relationship between adherence and clinical outcomes, the strength and consistency of these associations have not been fully elucidated and remain [...] Read more.

Background: Medication adherence is a critical component of effective management in type 2 diabetes mellitus (T2DM). Although previous studies have explored the relationship between adherence and clinical outcomes, the strength and consistency of these associations have not been fully elucidated and remain unclear. In particular, evidence derived from patient-reported measures of adherence is limited, and the prognostic significance of adherence as assessed from the patient perspective is not clearly defined. Methods: We conducted a prospective observational cohort study consisting of adult patients with T2DM who received regular outpatient follow-up. Medication adherence was assessed at the time of enrollment using the eight-item Morisky Medication Adherence Scale (MMAS-8) and was categorized as good, moderate, or poor. Participants were subsequently followed for five years to ascertain clinical outcomes. Primary outcomes were assessed longitudinally and included the occurrence of nonfatal myocardial infarction, heart failure, nonfatal stroke, and progression to end-stage kidney disease (ESKD), as well as all-cause mortality. Secondary outcomes included changes in glycated hemoglobin (HbA1c), estimated glomerular filtration rate (eGFR), and low-density lipoprotein (LDL) levels. Results: No statistically significant differences were observed in the incidence of nonfatal myocardial infarction, heart failure, nonfatal stroke, or progression to ESKD across adherence groups. In contrast, all-cause mortality was significantly higher among patients with poor adherence. With respect to metabolic outcomes, HbA1c and eGFR at five years were comparable across adherence groups, whereas LDL levels were significantly higher in patients with poor adherence. Conclusions: Poor medication adherence as assessed at baseline may be related to a higher risk of all-cause mortality and poorer lipid control, while no statistically significant differences were observed for nonfatal cardiovascular or renal outcomes. Full article

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

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24 pages, 3694 KB

Open AccessArticle

Electrospun PVA Nanofibers Co-Loaded with Atorvastatin and Zinc Oxide for Antibacterial and In Vitro Wound Healing Applications

by Rawan Fitaihi, Alanoud Altalal, Rihaf Alfaraj, Fai Alkathiri, Riyad F. Alzhrani, Shumukh Aldawsari, Shouq Alorayyidh, Meshal Alnefaie, Nojoud Al Fayez and Njoud Altuwaijri

Biomedicines 2026, 14(3), 724; https://doi.org/10.3390/biomedicines14030724 - 20 Mar 2026

Viewed by 753

Abstract

Background: The global rise in antimicrobial resistance (AMR) has created an urgent need for innovative antibacterial strategies and localized delivery systems. This study aimed to develop and characterize electrospun poly (vinyl alcohol) (PVA) nanofibers co-loaded with atorvastatin (ATR) and zinc oxide (ZnO) nanoparticles [...] Read more.

Background: The global rise in antimicrobial resistance (AMR) has created an urgent need for innovative antibacterial strategies and localized delivery systems. This study aimed to develop and characterize electrospun poly (vinyl alcohol) (PVA) nanofibers co-loaded with atorvastatin (ATR) and zinc oxide (ZnO) nanoparticles for use as a multifunctional topical platform for wound healing and infection control. Methods: ZnO nanoparticles were prepared via ball milling and characterized for size and zeta potential. Four PVA-based nanofiber formulations were fabricated using electrospinning: blank (F1), ZnO-loaded (F2), ATR-loaded (F3), and ATR/ZnO co-loaded (F4). The nanofibers were evaluated for morphology, thermal properties, crystallinity, and drug release. Antibacterial efficacy was tested against S. aureus, S. epidermidis, MRSA, and P. aeruginosa using broth microdilution and checkerboard assays. Biocompatibility and wound healing potential were assessed via MTT and fibroblast scratch assays on human foreskin fibroblasts (hFFs). Results: SEM imaging confirmed the production of uniform, bead-free nanofibers. ATR and ZnO nanoparticles were successfully incorporated in the nanofiber. The co-loaded formulation (F4) demonstrated a sustained release profile, releasing approximately 78.7% of ATR over 24 h. While all treatments showed limited activity against P. aeruginosa, the ATR/ZnO co-loaded nanofibers exhibited significantly enhanced antibacterial activity against Gram-positive strains, achieving the lowest MIC values (1.5–2.0 mg/mL). Synergy analysis confirmed an enhanced effect with ATR and ZnO against MRSA. Furthermore, F4 achieved the highest wound closure rate of 92.41% in 24 h while maintaining acceptable cytocompatibility. Conclusions: The integration of ATR and ZnO into PVA nanofibers provides an enhanced antibacterial effect consistent with the synergistic potential observed between free agents targeting Gram-positive wound pathogens. The platform’s ability to simultaneously inhibit bacterial growth and promote rapid fibroblast migration positions it as a promising localized therapeutic for managing infected wounds. Full article

(This article belongs to the Special Issue Drug Delivery and Nanocarrier)

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16 pages, 5649 KB

Open AccessArticle

Pan-Cancer Analysis Identifies SNORA12 as a Prognostic Biomarker and Demonstrates Its Role in Upregulating TIGIT in Osteosarcoma

by Weiwei He, Wenbo Shi, Qian Li, Baiguang Yu, Jia Song, Marina Igorevna Sekacheva and Haiyan Hu

Biomedicines 2026, 14(3), 723; https://doi.org/10.3390/biomedicines14030723 - 20 Mar 2026

Viewed by 889

Abstract

Background: Small nucleolar RNAs (snoRNAs) are emerging regulators of tumorigenesis, yet their pan-cancer landscape and immunological roles remain poorly defined. This study investigates the expression pattern, prognostic significance, and immune correlation of SNORA12 across cancers, with mechanistic validation in osteosarcoma. Methods: We integrated [...] Read more.

Background: Small nucleolar RNAs (snoRNAs) are emerging regulators of tumorigenesis, yet their pan-cancer landscape and immunological roles remain poorly defined. This study investigates the expression pattern, prognostic significance, and immune correlation of SNORA12 across cancers, with mechanistic validation in osteosarcoma. Methods: We integrated RNA-seq data from the TCGA, TARGET, and GTEx databases to evaluate SNORA12 expression and its prognostic value using Cox regression and Kaplan–Meier analyses (progression-free survival, PFS). The correlation between SNORA12 and the tumor immune microenvironment was assessed using six independent algorithms (TIMER, EPIC, CIBERSORT, IPS, MCP-counter, xCELL). In vitro, the regulatory effect of SNORA12 on the immune checkpoint TIGIT was validated by overexpression and knockdown experiments in osteosarcoma cell lines (SW1353, U2OS) and NK cells. Results: SNORA12 expression exhibited significant tumor-type specificity. High SNORA12 expression was associated with poor prognosis in glioma (HR = 1.31, p = 0.006) but favorable outcomes in pancreatic (HR = 0.51, p = 0.01) and breast cancer (HR = 0.56, p = 0.02). Immunologically, SNORA12 showed robust positive correlations with CD8+ T cell infiltration in thyroid carcinoma (THCA) and lung adenocarcinoma (LUAD) across multiple algorithms. Notably, SNORA12 expression was positively correlated with m6A modifiers METTL3 and YTHDF1, and negatively correlated with the demethylase FTO. Experimentally, overexpression of SNORA12 in osteosarcoma cells and primary NK cells significantly upregulated TIGIT at both the mRNA and protein levels, while SNORA12 knockdown in NK92 cells reduced TIGIT expression. Conclusions: This pan-cancer analysis positions SNORA12 as a tumor type-specific prognostic biomarker and reveals its novel role as a positive regulator of TIGIT in osteosarcoma, offering a potential mechanistic link between snoRNA dysregulation and immune evasion. Full article

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

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17 pages, 1485 KB

Open AccessArticle

A Pilot Study Investigating Clinical and Functional Outcomes of Novel Double-Coil rPMS in Knee Osteoarthritis

by Roman Bednár, Martina Flašková and Nicole Fejková

Biomedicines 2026, 14(3), 722; https://doi.org/10.3390/biomedicines14030722 - 20 Mar 2026

Cited by 2 | Viewed by 710

Abstract

Background: Knee osteoarthritis (KOA) is one of the leading causes of chronic pain and long-term disability worldwide. Despite its high prevalence, KOA remains underrepresented in repetitive peripheral magnetic stimulation (rPMS) research. While total knee arthroplasty remains the definitive treatment, there is a growing [...] Read more.

Background: Knee osteoarthritis (KOA) is one of the leading causes of chronic pain and long-term disability worldwide. Despite its high prevalence, KOA remains underrepresented in repetitive peripheral magnetic stimulation (rPMS) research. While total knee arthroplasty remains the definitive treatment, there is a growing need for non-invasive approaches to reduce symptoms in patients seeking conservative alternatives or awaiting surgery. Methods: Thirty patients with KOA underwent a non-invasive treatment program consisting of eight sessions of double-coil repetitive peripheral magnetic stimulation (rPMS) over three weeks. Outcome measures included pain intensity assessed by the Visual Analog Scale (VAS), functional ability evaluated by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and the Timed Up and Go test (TUG), and joint mobility measured as knee flexion and extension. Clinical relevance was evaluated using the Minimal Clinically Important Difference (MCID), and subgroup analyses were performed according to Kellgren-Lawrence (KL) grade. Results: Double-coil rPMS was associated with statistically and clinically significant improvements in all outcomes. MCID responder rates exceeded 80% for VAS and TUG, exceeded 70% for WOMAC, and approached 50% for joint mobility outcomes. Subgroup analysis indicated that patients with lower KL grades experienced greater pain reduction, whereas those with higher grades showed greater functional gains. Conclusions: Double-coil rPMS provided preliminary evidence of potential clinical benefit as a non-invasive approach in patients with KOA. Given the single-arm pilot design, the findings should be interpreted cautiously and require confirmation in adequately powered randomized controlled trials with longer follow-up. Full article

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

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17 pages, 490 KB

Open AccessReview

The Impact of Diabetes on Brain Health in Childhood

by László Barkai

Biomedicines 2026, 14(3), 721; https://doi.org/10.3390/biomedicines14030721 - 20 Mar 2026

Viewed by 754

Abstract

Background/Objectives: The global incidence of diabetes in childhood is increasing, raising concern about its long-term effects on the developing brain. Although paediatric diabetes research has traditionally focused on microvascular and macrovascular complications, accumulating evidence indicates that the brain is also a vulnerable target. [...] Read more.

Background/Objectives: The global incidence of diabetes in childhood is increasing, raising concern about its long-term effects on the developing brain. Although paediatric diabetes research has traditionally focused on microvascular and macrovascular complications, accumulating evidence indicates that the brain is also a vulnerable target. Methods: This narrative review synthesizes current knowledge on the impact of diabetes on brain health in children and adolescents, with emphasis on epidemiology, neuroimaging and cognitive outcomes, underlying mechanisms, risk and protective factors, and clinical implications. Results: In type 1 diabetes (T1D), studies consistently demonstrate subtle but measurable alterations in brain structure, including reduced growth of total, grey, and white matter volumes, alongside functional and microstructural changes. These neurobiological differences are associated with mild deficits in cognition, particularly in attention, executive function, memory, and processing speed. While clinically significant impairment affects a minority, subclinical alterations are common and may accumulate over time. Key risk factors include chronic hyperglycaemia, glycaemic variability, severe hypoglycaemia, diabetic ketoacidosis, and younger age at onset, whereas good glycaemic stability, diabetes technologies, supportive psychosocial environments, and adequate sleep appear protective. Proposed mechanisms involve oxidative stress, neuroinflammation, disrupted insulin signalling, altered cerebral metabolism, and vulnerability of the immature brain during critical developmental windows. Type 2 diabetes (T2D), increasingly diagnosed in youth, is also associated with adverse brain outcomes. Emerging data link early-onset T2D to alterations in brain structure and connectivity, poorer cognitive performance, and increased mental health burden, mediated by hyperglycaemia, insulin resistance, inflammation, and psychosocial stressors. Conclusions: Overall, childhood diabetes—both T1D and T2D—is associated with meaningful effects on brain development and function. Longitudinal and interventional studies are needed to establish causality and determine whether optimizing glycaemic control and psychosocial support can mitigate neurocognitive risk. Recognizing brain health as a potential complication of paediatric diabetes has important implications for monitoring, prevention, and clinical care. Full article

(This article belongs to the Special Issue Pathology, Complications, and Prognosis of Type 1 Diabetes (T1D))

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11 pages, 1117 KB

Open AccessArticle

Serum Protein Electrophoresis and the Albumin-to-Globulin Ratio in the Differential Diagnosis of Minimal Change Disease and Focal Segmental Glomerulosclerosis

by László Bitó, Tamás Lantos, Krisztina Jost, Amir Reza Manafzadeh, Béla Iványi and Levente Kuthi

Biomedicines 2026, 14(3), 720; https://doi.org/10.3390/biomedicines14030720 - 20 Mar 2026

Viewed by 724

Abstract

Background/Objectives: Differentiating minimal change disease (MCD) from focal segmental glomerulosclerosis (FSGS) remains a diagnostic challenge. We hypothesised that differences in glomerular protein selectivity could translate into distinct serum protein electrophoresis (SPEP) profiles, particularly in severe nephrotic syndrome. Methods: We retrospectively analysed SPEP profiles [...] Read more.

Background/Objectives: Differentiating minimal change disease (MCD) from focal segmental glomerulosclerosis (FSGS) remains a diagnostic challenge. We hypothesised that differences in glomerular protein selectivity could translate into distinct serum protein electrophoresis (SPEP) profiles, particularly in severe nephrotic syndrome. Methods: We retrospectively analysed SPEP profiles of adults with biopsy-proven MCD (n = 27), primary FSGS (n = 27), and secondary FSGS (n = 20). Diagnoses were established according to KDIGO guidelines and the Mayo Clinic classification. A severe subgroup was defined by a relative albumin fraction <40% to evaluate patterns in marked hypoalbuminaemia. Results: Secondary FSGS demonstrated significantly higher albumin-to-globulin (A/G) ratios compared with immune-mediated podocytopathies (MCD and primary FSGS), yielding excellent discrimination (AUC > 0.98). In contrast, discriminatory performance between MCD and primary FSGS in the overall cohort was limited (AUC = 0.657). However, within the severe subgroup, the A/G ratio provided clinically meaningful separation (AUC = 0.787). An A/G ratio > 0.49 identified primary FSGS with 86.7% sensitivity and 81.2% specificity. Correlation analysis revealed a strong inverse association between albumin and α2-globulin fractions in immune-mediated podocytopathies (ρ < −0.8), whereas this relationship was attenuated in secondary FSGS (ρ = −0.57). Conclusions: The A/G ratio may represent a practical adjunctive biomarker in the evaluation of podocytopathies. Values > 1.0 strongly favour secondary FSGS, while markedly reduced ratios in severe nephrosis are characteristic of MCD. These findings suggest that differences in glomerular selectivity and the hepatic compensatory response are reflected in routine electrophoretic profiles. Full article

(This article belongs to the Special Issue Nephrotic Syndrome: Pathomechanism, Diagnostics and Novel Treatment Options—2nd Edition)

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17 pages, 3189 KB

Open AccessArticle

Combined Antineoplastic Effects of Metformin, Boric Acid and Resveratrol in SKOV3 Ovarian Cancer Cells

by Burcu Biltekin, Mete Hakan Karalok, Seyma Dumur, Naile Fevziye Mısırlıoglu and Hafize Uzun

Biomedicines 2026, 14(3), 719; https://doi.org/10.3390/biomedicines14030719 - 20 Mar 2026

Cited by 1 | Viewed by 613

Abstract

Background: Ovarian cancer (OC) is characterized by aggressive progression, high metastatic potential, and frequent resistance to conventional chemotherapy, highlighting the need for novel combination-based therapeutic strategies. Metformin has emerged as a promising antineoplastic agent; however, its efficacy may be enhanced through combination with [...] Read more.

Background: Ovarian cancer (OC) is characterized by aggressive progression, high metastatic potential, and frequent resistance to conventional chemotherapy, highlighting the need for novel combination-based therapeutic strategies. Metformin has emerged as a promising antineoplastic agent; however, its efficacy may be enhanced through combination with bioactive compounds. This study aimed to investigate the antineoplastic effects of metformin in SKOV3 human OC cells and to evaluate whether these effects could be potentiated by boric acid (BA) and resveratrol, with particular emphasis on their modulatory impact on key inflammatory and tumor-associated biomarkers, including interleukin-17 (IL-17), nuclear factor kappa-B (NF-κB), and midkine (MDK). Methods: SKOV3 cells were treated with metformin, BA, and resveratrol as monotherapies or in combination. Cell viability was assessed using a colorimetric assay, while migratory capacity was evaluated by wound healing analysis. The expression levels of IL-17, NF-κB, and MDK were quantified in cell lysates, and p21 protein expression was analyzed by immunocytochemistry. Results: All treatments induced concentration- and time-dependent reductions in cell viability. Combination treatments, particularly metformin with boric acid or resveratrol, produced more pronounced inhibitory effects on cell survival and migration compared with single-agent treatments. Inflammatory and tumor-associated biomarkers, including IL-17, NF-κB, and MDK, were significantly modulated following treatment. Additionally, increased p21 expression was observed in treated cells, indicating enhanced cell cycle regulatory activity. Conclusions: These findings indicate that BA and resveratrol enhance the antineoplastic activity of metformin in SKOV3 OC cells by suppressing proliferative and migratory capacities and modulating inflammatory mediators such as IL-17, NF-κB, and MDK. However, since toxicity assessments in non-cancerous cells were not performed, the safety profile of this combination remains unclear and requires further investigation in non-cancerous models. Full article

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

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21 pages, 706 KB

Open AccessArticle

Rheopheresis, but Not Phlebotomy, Improves Cerebral Vascular Response to Hypercapnia and Neuronal Activation

by Dóra Sulina, Szonja Krisztina Rab-Bábel, Ádám Varga, Ádám Attila Mátrai, Kristóf Gál, Pál Soltész, Norbert Németh and László Oláh

Biomedicines 2026, 14(3), 718; https://doi.org/10.3390/biomedicines14030718 - 20 Mar 2026

Viewed by 703

Abstract

Background/Objectives: Several therapeutic approaches, including phlebotomy and rheopheresis, are used to improve hemorheological parameters. While the effects of phlebotomy on cerebral circulation have been described, the impact of rheopheresis on cerebral hemodynamics remains poorly understood. This study primarily aimed to evaluate the [...] Read more.

Background/Objectives: Several therapeutic approaches, including phlebotomy and rheopheresis, are used to improve hemorheological parameters. While the effects of phlebotomy on cerebral circulation have been described, the impact of rheopheresis on cerebral hemodynamics remains poorly understood. This study primarily aimed to evaluate the within-group effects of phlebotomy and rheopheresis on cerebral blood flow velocity changes evoked by neuronal activation and on cerebrovascular reactivity in patients with elevated hematocrit or hyperviscosity, respectively. Methods: In our present study, we used transcranial Doppler to examine the effects of phlebotomy (n = 11) and rheopheresis (n = 9) on cerebral hemodynamics in patients with elevated hematocrit and hyperviscosity, respectively. Measurements included resting flow velocity (FV) in the posterior cerebral artery (PCA) and middle cerebral artery (MCA), the visually evoked FV response in the PCA (neurovascular coupling) and the hypercapnia-induced FV response in the MCA (cerebral vasoreactivity). In addition to flow velocity data, visual evoked potential (VEP) parameters were also recorded to assess neuronal activation. Results: Phlebotomy significantly reduced hematocrit and hemoglobin levels, while rheopheresis led to a significant decrease in both blood and plasma viscosity. Although we observed no differences in resting FV values before and after either intervention, the FV increase in response to visual stimulation and hypercapnia was greater after rheopheresis than before, whereas no such difference was observed following phlebotomy. VEP parameters remained similar before and after both phlebotomy and rheopheresis. Conclusions: Our data indicate that rheopheresis reduces blood and plasma viscosity in patients with hyperviscosity and leads to a significant improvement in cerebral vasoreactivity and neurovascular coupling, without affecting VEP parameters. The improvement in cerebral vasoreactivity, but no changes in VEP parameters, suggests that the improved FV response to visual stimulation after rheopheresis is most likely caused by better vascular response rather than improved neuronal activation. Full article

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

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16 pages, 251 KB

Open AccessArticle

Anthracycline-Free Neoadjuvant Pertuzumab–Trastuzumab–Taxane in Patients with HER2-Positive Early Breast Cancer: Hormone Receptor Status as a Key Determinant of Pathological Complete Response

by Azzurra Irelli, Tina Sidoni, Francesco Pavese, Silvia Rotondaro, Carla Luzi, Veronica Zelli, Sara Centonze, Leonardo Valerio Patruno, Francesca Zazzeroni, Alessandra Tessitore and Katia Cannita

Biomedicines 2026, 14(3), 717; https://doi.org/10.3390/biomedicines14030717 - 20 Mar 2026

Cited by 1 | Viewed by 680

Abstract

Background: Neoadjuvant chemotherapy plus dual HER2 blockade is standard for HER2-positive early breast cancer (EBC), but the impact of hormone receptor (HR) status and PIK3CA mutations with anthracycline-free regimens remains unclear. Methods: We retrospectively analyzed 56 patients with stage II–III HER2-positive [...] Read more.

Background: Neoadjuvant chemotherapy plus dual HER2 blockade is standard for HER2-positive early breast cancer (EBC), but the impact of hormone receptor (HR) status and PIK3CA mutations with anthracycline-free regimens remains unclear. Methods: We retrospectively analyzed 56 patients with stage II–III HER2-positive EBC treated with neoadjuvant pertuzumab–trastuzumab–taxane (THP) at a single institution. Pathological complete response (pCR, ypT0/is ypN0) was the primary endpoint; secondary endpoints were safety and early disease-free/overall survival (DFS/OS), while associations of HR status and PIK3CA mutations with pCR were explored. Results: The overall pCR rate was 60.7%, in line with major dual-HER2 neoadjuvant trials. HR-negative patients achieved higher pCR rates than HR-positive patients (85.7% vs. 45.7%; p = 0.007; odds ratio 7.125), identifying HR status as the main clinical factor associated with response. Among 36 patients with PIK3CA testing, pCR rates appeared similar in mutated and wild-type tumors (62.5% vs. 60.7%), but the small number of mutated cases precludes firm conclusions. At a median follow-up of 42 months, only five DFS and one OS event had occurred, so survival analyses are exploratory and should be interpreted cautiously. THP demonstrated an excellent safety profile, with minimal grade 3–4 toxicity, and no clinically relevant hematological, cardiac, or pulmonary events. Conclusions: Anthracycline-free THP is a highly active, well-tolerated neoadjuvant option for HER2-positive EBC, with particularly high pCR rates in HR-negative disease. HR status emerged as a key determinant of pCR, whereas the role of PIK3CA mutations remains inconclusive and requires confirmation in larger prospective studies. Full article

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

12 pages, 618 KB

Open AccessArticle

Predicting 1-Year Trifecta Outcomes After High-Intensity Focused Ultrasound and Cryoablation for Low- and Intermediate-Risk Prostate Cancer

by Umberto Anceschi, Antonio Tufano, Gabriele Tuderti, Riccardo Mastroianni, Simone D’Annunzio, Maria Consiglia Ferriero, Flavia Proietti, Lorenzo Capecchi, Giuseppe Spadaro, Maddalena Iori, Leonardo Misuraca, Franco Lugnani and Giuseppe Simone

Biomedicines 2026, 14(3), 716; https://doi.org/10.3390/biomedicines14030716 - 20 Mar 2026

Cited by 1 | Viewed by 653

Abstract

Objectives: Focal therapy (FT) is increasingly employed in selected patients with localized prostate cancer (PCa), aiming to balance oncologic control with preservation of urinary and sexual function. Among the available energy sources, prostate gland cryoablation (PGC) and high-intensity focused ultrasound (HIFU) are [...] Read more.

Objectives: Focal therapy (FT) is increasingly employed in selected patients with localized prostate cancer (PCa), aiming to balance oncologic control with preservation of urinary and sexual function. Among the available energy sources, prostate gland cryoablation (PGC) and high-intensity focused ultrasound (HIFU) are the most widely adopted techniques. However, comparative outcome data remain limited, and standardized composite endpoints are still lacking in this domain. Methods: We conducted a prospective, single-center study on 163 consecutive patients treated with FT, either HIFU (n = 49) or PGC (n = 114), for clinically localized PCa between 2019 and 2024. The primary aim was to compare baseline, perioperative, oncologic, and functional outcomes at 1-year follow-up. The secondary objective was to identify predictors of trifecta achievement, defined as: (1) absence of treatment failure; (2) urinary continence (no pads or one safety pad/day); and (3) recovery of erectile function comparable to baseline. Results: HIFU was associated with shorter operative time (p = 0.04) but required longer catheterization (p < 0.001). Compared with HIFU, primary whole-gland cryoablation (PGC) showed a higher overall complication rate (p < 0.001), mostly grade I–II events. Median follow-up was shorter for HIFU (12 vs. 23 months, p < 0.001). Further, 1-year treatment failure occurred in 8.1% of HIFU cases and 8.7% of PGC cases (p = 0.96), although failure-free survival was comparable between groups (p = 0.89). Functional outcomes were similar, with no significant differences in continence or potency recovery, and trifecta rates were 38.9% (HIFU) vs. 37.4% (PGC; p = 0.355). On multivariable analysis, hypertension, lower PSA, higher baseline erectile function, and unilateral ablation independently predicted trifecta achievement. Conclusions: In this prospective comparison between HIFU and PGC, we observed similar trifecta achievement rates, with no significant differences in continence or erectile function recovery at 1 year. Although treatment failure was slightly more frequent after HIFU, overall outcomes support the functional safety and oncologic feasibility of both approaches in selected patients. These findings suggest that adopting a standardized composite endpoint may be clinically useful, even if further refinement and validation are still needed to capture the specific goals and nuances of focal therapy. Full article

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

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9 pages, 363 KB

Open AccessArticle

Progressive Aortic Regurgitation After Impella Bridge-to-LVAD: A Two-Year Cohort Analysis

by Attila Nemeth, Aron Frederik Popov, Rodrigo Sandoval Boburg, Spiros Lukas Marinos, Helene Häberle, Christoph Salewski, Volker Steger, Christian Schlensak and Medhat Radwan

Biomedicines 2026, 14(3), 715; https://doi.org/10.3390/biomedicines14030715 - 19 Mar 2026

Viewed by 629

Abstract

Background/Objectives: Impella support is increasingly utilized as a crucial bridge to durable left ventricular assist device (LVAD) in patients with refractory cardiogenic shock. However, the transvalvular path of the Impella catheter raises concerns regarding mechanical trauma, potentially precipitating or accelerating aortic regurgitation [...] Read more.

Background/Objectives: Impella support is increasingly utilized as a crucial bridge to durable left ventricular assist device (LVAD) in patients with refractory cardiogenic shock. However, the transvalvular path of the Impella catheter raises concerns regarding mechanical trauma, potentially precipitating or accelerating aortic regurgitation (AR). We aimed to characterize the complete longitudinal trajectory of AR following Impella bridge-to-LVAD and to determine its association with clinical and hemodynamic sequelae. Methods: We conducted a single-center retrospective cohort study including all patients bridged from Impella to durable LVAD between 2013 and 2024 (n = 19). At Impella initiation, all patients met the retrospective SCAI shock stage D or worse criteria. At LVAD implantation, all patients were classified as INTERMACS 1–2 (INTERMACS 2, n = 13). The Impella models were 5.0 in 11 (axillary access), 2.5 in 5 (femoral access), and CP in 3 (femoral access); no periprocedural Impella complications were recorded. The implanted LVAD systems were HeartMate II (n = 7), HVAD (n = 3), and HeartMate III (n = 9). Patients undergoing concomitant aortic valve intervention were excluded. Transthoracic/TEE echocardiography was performed at prespecified time points (pre-Impella, pre-LVAD, post-LVAD discharge, 12 months, and 24 months) with standardized aortic regurgitation (AR) grading. Right ventricular (RV) function was assessed qualitatively when quantitative indices (TAPSE) were unavailable. Primary endpoints were new or progressive AR and AR severity at LVAD implantation. Secondary endpoints included survival, renal dysfunction, biomarkers, and rehospitalization. Univariate analyses were used to compare outcomes according to AR severity. Results: Nineteen patients (68% male, median age 57 years, IQR 47–60) underwent Impella support for 13.3 ± 9.9 days before HeartMate 3 (84%) or HVAD (16%) implantation. All patients had competent aortic valves (grade 0 AR) at the time of LVAD implantation. AR ≥ mild developed in 9/18 (50%) at discharge, 12/15 (80%) at 12 months, and 13/15 (87%) at 24 months, and 8/15 (53%) progressed to ≥ moderate AR by 24 months. Patients with moderate-to-severe AR had higher NT-proBNP levels at 12 months (median 6318 vs. 2336 pg/mL, p = 0.137). Thirty-day and 24-month survival rates were 95% and 79%, respectively. Conclusions: Aortic regurgitation frequently develops or progresses from the pre-LVAD period to follow-up in patients bridged from Impella to durable LVAD. Although limited by a small sample size and incomplete quantitative RV metrics, these observations support structured echocardiographic surveillance after Impella use and management strategies—routine valve inspection at LVAD implantation and post-LVAD speed/blood pressure targets that encourage aortic valve opening—to mitigate the risk and clinical impact of aortic regurgitation. Full article

(This article belongs to the Special Issue Acute and Chronic Heart Failure: Pathophysiology and New Therapeutic Developments, 3rd Edition)

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28 pages, 16544 KB

Open AccessArticle

Ferulic Acid Alleviates Chemotherapy-Induced POI by Targeting the Grp78 and Perk-eIF2α-ATF4-CHOP Pathway to Attenuate Endoplasmic Reticulum Stress

by Fan Li, Yanjing Huang, Zhuo Liu, Yuli Geng, Runan Hu, Yufan Song, Lijun Xu and Mingmin Zhang

Biomedicines 2026, 14(3), 714; https://doi.org/10.3390/biomedicines14030714 - 19 Mar 2026

Viewed by 816

Abstract

Backgrounds: Premature ovarian insufficiency (POI) is a clinical syndrome characterized by premature ovarian dysfunction, amenorrhea, and infertility. Ferulic acid (FA) is a prominent bioactive phenolic compound derived from traditional Chinese herbs Angelica sinensis (Oliv.) Diels and Ligusticum chuanxiong Hort. These herbs are [...] Read more.

Backgrounds: Premature ovarian insufficiency (POI) is a clinical syndrome characterized by premature ovarian dysfunction, amenorrhea, and infertility. Ferulic acid (FA) is a prominent bioactive phenolic compound derived from traditional Chinese herbs Angelica sinensis (Oliv.) Diels and Ligusticum chuanxiong Hort. These herbs are commonly used to treat gynecological disorders including menstrual irregularities and infertility, and are known to modulate endoplasmic reticulum (ER) stress. However, the therapeutic potential and molecular mechanisms of FA in the context of POI remain largely unexplored. This study aimed to investigate the protective effects of FA against POI and to elucidate the underlying pharmacological mechanisms. Methods: In vivo, a mouse model of POI was established via a single intraperitoneal injection of cyclophosphamide (CTX; 120 mg/kg), and using FA for 28 days of continuous gavage to observe its therapeutic effect. Ovarian function and pathological changes were assessed by hormone levels, follicle development and oxidative stress (OS) level. In vitro, the effects of FA were examined using 4-hydroperoxy cyclophosphamide (4-OHCP)-treated KGN granulosa cells. Transcriptome sequencing, molecular docking, and molecular dynamics simulations were employed to identify potential targets of FA. Results: Our findings demonstrated that FA administration helped preserve regular estrous cycles, promoted follicle development and hormone secretion, and attenuated OS in both ovarian tissue and granulosa cells (GCs). Transcriptomic profiling combined with molecular docking and molecular dynamics simulations suggested that FA potentially targets key ER stress proteins, specifically Grp78 and Perk. Further in vivo and in vitro experiments confirmed that FA alleviates ER stress by inhibiting the overactivation of the Perk/eIF2α/ATF4/CHOP signaling pathway. Notably, the protective effects of FA were comparable to those of the ER stress inhibitor 4-Phenylbutyric acid (4-PBA) and were reversed by the ER stress activator tunicamycin (TM). Additionally, FA downregulates ERO1α expression, further blocking secondary oxidative damage triggered by ER stress. In KGN cells, FA significantly inhibits 4-OHCP-induced apoptosis and upregulates the anti-apoptotic proteins BCL-2 and BCL-xL, exhibiting efficacy similar to 4-PBA. Conclusions: FA improves ovarian function in CTX-induced POI by coordinately regulating OS and ER stress, inhibiting the Perk/eIF2α/ATF4/CHOP pathway, and suppressing GC apoptosis. These findings provide experimental evidence supporting FA as a potential therapeutic candidate for POI. Full article

(This article belongs to the Special Issue Natural Product for the Interventions of Chronic Diseases: From Source to Therapy)

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25 pages, 2531 KB

Open AccessArticle

FedIHRAS: A Privacy-Preserving Federated Learning Framework for Multi-Institutional Collaborative Radiological Analysis with Integrated Explainability and Automated Clinical Reporting

by André Luiz Marques Serrano, Gabriel Arquelau Pimenta Rodrigues, Guilherme Dantas Bispo, Vinícius Pereira Gonçalves, Geraldo Pereira Rocha Filho, Maria Gabriela Mendonça Peixoto, Rodrigo Bonacin and Rodolfo Ipolito Meneguette

Biomedicines 2026, 14(3), 713; https://doi.org/10.3390/biomedicines14030713 - 19 Mar 2026

Viewed by 596

Abstract

Background/Objectives: Federated learning has emerged as a promising paradigm for enabling collaborative artificial intelligence in healthcare while preserving data privacy. However, most existing frameworks focus on isolated tasks and lack integrated pipelines that combine classification, segmentation, explainability, and automated clinical reporting. Methods: This [...] Read more.

Background/Objectives: Federated learning has emerged as a promising paradigm for enabling collaborative artificial intelligence in healthcare while preserving data privacy. However, most existing frameworks focus on isolated tasks and lack integrated pipelines that combine classification, segmentation, explainability, and automated clinical reporting. Methods: This study proposes FedIHRAS, a privacy-preserving federated learning framework designed for multi-institutional radiological analysis. The system integrates multi-task deep learning modules, including pathology classification using a modified ResNet-50 backbone, anatomical segmentation, explainability through Grad-CAM, and automated report generation supported by semantic aggregation using SNOMED CT. The framework employs confidence-weighted aggregation, differential privacy mechanisms, and secure aggregation protocols to ensure privacy and robustness across heterogeneous institutional datasets. Results: Experimental evaluation was conducted across four large-scale chest X-ray datasets representing simulated institutional nodes, totaling approximately 874,000 images. FedIHRAS achieved high diagnostic performance with strong cross-institutional generalization and demonstrated improved robustness under non-IID data distributions. Additional experiments showed favorable communication efficiency, effective privacy–utility trade-offs, and strong agreement with expert radiologist assessments. Conclusion: The proposed FedIHRAS framework demonstrates that federated learning can support scalable, privacy-preserving, and clinically meaningful radiological AI systems. By integrating multi-task learning, explainability, and automated reporting within a unified federated architecture, the framework addresses key limitations of existing approaches and contributes to the development of collaborative AI in healthcare. Full article

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

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14 pages, 2911 KB

Open AccessArticle

Primary Cilia Are Required for Efficient BMP Signaling in Traumatic Heterotopic Ossification

by Xinyuan Yuan, Saman Toutounchi, Susan F. Law, David Achudhan, Abhishek Chandra, Kai He, Yingshu Cao, Jinghua Hu, Robert J. Pignolo and Haitao Wang

Biomedicines 2026, 14(3), 712; https://doi.org/10.3390/biomedicines14030712 - 19 Mar 2026

Viewed by 727

Abstract

Background/Objectives: Heterotopic ossification (HO), the aberrant formation of bone within soft tissues, arises either from rare genetic mutations or more commonly from traumatic insults. It is a major cause of morbidity not only in individuals harboring causative mutations, but also in those undergoing [...] Read more.

Background/Objectives: Heterotopic ossification (HO), the aberrant formation of bone within soft tissues, arises either from rare genetic mutations or more commonly from traumatic insults. It is a major cause of morbidity not only in individuals harboring causative mutations, but also in those undergoing musculoskeletal surgery or trauma and in soldiers sustaining blast or burn injuries. Bone morphogenetic protein (BMP) signaling is a central driver of both hereditary and acquired forms of HO. Primary cilia are nonmotile, antenna-like organelles that extend from the cell surface and serve as crucial sensory and signaling hubs by concentrating key pathway components within a confined volume at the ciliary tip. However, their functional role in the pathogenesis of traumatic HO remains poorly understood. Methods: We investigate the role of primary cilia in traumatic HO using a genetically modified mouse model and cellular model. Results: We demonstrate that BMP signaling is attenuated when primary cilia function is disrupted. Both ciliation frequency and ciliary length were reduced in Scleraxis-CreERT2; Intraflagellar transport 88 ^{floxed/floxed} (Scx-CreERT2;Ift88^fl/fl) tenocytes. Deletion of Ift88 effectively suppressed pathological BMP signaling and inhibited HO formation. Conclusions: These findings establish that functional primary cilia are required for traumatic HO development and highlight ciliary regulation as a potential therapeutic avenue for preventing or mitigating post-traumatic HO. Full article

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

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22 pages, 1289 KB

Open AccessReview

Advances in SRNS Gene Research: From Precision Classification to Precision Diagnosis and Treatment

by Yuhong Ye, Limin Huang, Haidong Fu, Jingjing Wang and Yanyan Jin

Biomedicines 2026, 14(3), 711; https://doi.org/10.3390/biomedicines14030711 - 19 Mar 2026

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Abstract

To clarify the genetic classification, diagnostic strategies, and precision treatment pathways of steroid-resistant nephrotic syndrome (SRNS), this review systematically reviews the genetic stratification system of SRNS by integrating recent advances in genetic testing technologies and pathogenesis research. It contains the pathogenic mechanisms, diagnostic [...] Read more.

To clarify the genetic classification, diagnostic strategies, and precision treatment pathways of steroid-resistant nephrotic syndrome (SRNS), this review systematically reviews the genetic stratification system of SRNS by integrating recent advances in genetic testing technologies and pathogenesis research. It contains the pathogenic mechanisms, diagnostic protocols, and therapeutic correlations of different genetic subtypes, while summarizing current progress and clinical challenges in gene therapy. Results indicate SRNS can be categorized into genetic (38–58%) and non-genetic/immune-mediated (40–60%). A stepwise diagnostic system comprising core proteinuria gene panel testing, whole-genome sequencing (WGS), whole-exome sequencing (WES), and supplementary multi-omics/long-range sequencing is proposed, suited for populations with “typical phenotypes and moderate genetic risk”, “atypical phenotypes and high genetic suspicion”, and “complex structural/non-coding region variants” respectively. Pathogenic mechanisms directly determine therapeutic strategies: COQ2/PDSS2 mutations respond to coenzyme Q10 suplementation, while NPHS1 mutations necessitate early renal transplantation. Adeno-associated virus (AAV)-mediated gene therapy and CRISPR-Cas editing show preclinical promise but face challenges including incomplete detection coverage and clinical translation difficulties. Genetic technologies are driving SRNS management transformation from “empirical treatment” to “mechanism-oriented precision diagnosis and therapy”. Future efforts should focus on overcoming genetic testing limitations and gene therapy translation bottlenecks to enhance diagnostic and therapeutic efficacy. Full article

(This article belongs to the Special Issue Emerging Trends in Kidney Disease (2nd Edition))

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22 pages, 3397 KB

Open AccessReview

Advances in Bone-on-a-Chips for In Vitro Modeling of Bone Physiology and Pathology

by Xiuyun Cheng, Mingxia Lu, Ming Ma, Shumin Zhou, Jun Xu, Yuhao Li and Hongxu Lu

Biomedicines 2026, 14(3), 710; https://doi.org/10.3390/biomedicines14030710 - 19 Mar 2026

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Abstract

Bone is a dynamic and multifunctional tissue that provides mechanical support, regulates mineral homeostasis, supports hematopoiesis, and relies on complex interactions among multiple cell types. The increasing incidence of bone-related diseases, such as osteoporosis, osteoarthritis, fracture non-union, and bone cancer, highlights the need [...] Read more.

Bone is a dynamic and multifunctional tissue that provides mechanical support, regulates mineral homeostasis, supports hematopoiesis, and relies on complex interactions among multiple cell types. The increasing incidence of bone-related diseases, such as osteoporosis, osteoarthritis, fracture non-union, and bone cancer, highlights the need for in vitro models that better reflect human bone physiology. Bone-on-a-chip technology, developed through advances in microfluidics, biomaterials, and tissue engineering, offers a promising approach to recreate key features of the bone microenvironment in vitro. By incorporating bone-mimicking materials, relevant bone cells, vascular components, fluid perfusion, and mechanical stimulation, these platforms allow more realistic investigation of bone remodeling, regeneration, disease mechanisms, and drug responses. In parallel, bone organoids and their integration with microfluidic chips have further expanded the capabilities of in vitro bone models by enabling the formation of self-organized, human-relevant bone tissues with increased cellular complexity. This review summarizes recent progress in bone-on-a-chip systems, including models for osteogenesis and bone regeneration, vascularized bone, bone marrow and hematopoietic niches, cancer bone metastasis, and mechanobiological studies. Key design principles, materials, cellular components, and applications in disease modeling, drug screening, toxicity assessment, and personalized medicine are discussed. Current challenges and future directions are also discussed to support the continued development of more physiologically relevant in vitro bone models. Full article

(This article belongs to the Special Issue Applications of Biomedical Engineering and Biomaterials in Human Diseases)

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14 pages, 932 KB

Open AccessArticle

Management and Prognosis of Anti-MDA5 Dermatomyositis: Insights from a National Multicenter Cohort

by Sándor Mogyoróssy, Zoltán Griger, Tünde Tarr, Éva Zöld, György Pfliegler, Boglárka Csilla Brúgós, György Nagy, Károly Zsolt Mangel, Gábor Kumánovics, Rita Bakai, László Kovács, Adrienn Rideg, Edit Nagy, Orsolya Farkas, Gábor Nagy, Péter Antal-Szalmás, Gabriella Szűcs, Szilvia Szamosi, Zoltán Szekanecz, Éva Rákóczi and Levente Bodoki Show full author list Hide full author list

Biomedicines 2026, 14(3), 709; https://doi.org/10.3390/biomedicines14030709 - 19 Mar 2026

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Abstract

Background: Anti-melanoma differentiation-associated gene 5 (anti-MDA5) positive dermatomyositis is a distinct subset of idiopathic inflammatory myopathies (IIMs), often associated with unique cutaneous features and interstitial lung disease (ILD). While East Asian cohorts frequently report high mortality due to rapidly progressive ILD (RP-ILD), [...] Read more.

Background: Anti-melanoma differentiation-associated gene 5 (anti-MDA5) positive dermatomyositis is a distinct subset of idiopathic inflammatory myopathies (IIMs), often associated with unique cutaneous features and interstitial lung disease (ILD). While East Asian cohorts frequently report high mortality due to rapidly progressive ILD (RP-ILD), data regarding Central and Eastern European populations remain scarce. Methods: We conducted a retrospective multicenter study of anti-MDA5 positive Caucasian patients managed at four Hungarian rheumatology centers between 2020 and 2025. Demographic, clinical, serological, and radiological data were analyzed. Antibody profiling was performed using a standardized 16-antigen immunoblot assay. Results: Anti-MDA5 positivity was confirmed in 24 out of 742 patients (3.23%) treated in the four centers. The median age at diagnosis was 49.5 years (range: 24–81). Classic dermatomyositis was the predominant clinical phenotype (75%), followed by clinically amyopathic dermatomyositis (CADM) (12.5%) and polymyositis (12.5%). ILD was identified in 58.3% of patients, presenting with organizing pneumonia (OP), non-specific interstitial pneumonia (NSIP), and usual interstitial pneumonia (UIP) patterns. At diagnosis, median creatine kinase (CK) (193.5 U/L) and C-reactive protein (CRP) (4.24 mg/L) levels remained low even in the ILD group, whereas lactate dehydrogenase (LDH) was elevated in 91.7% of the cohort. Anti-Ro52 positivity (45.8% overall) emerged as a notable predictor of ILD (odds ratio [OR]: 22.5, 95% confidence interval [CI]: 2.10–240.48; p = 0.0045), being present in 71.4% of affected patients. RP-ILD occurred in two patients (8.3%). Therapeutic management followed an early, aggressive strategy, frequently utilizing cyclophosphamide (45.8%) and methotrexate (37.5%), with Janus kinase (JAK) inhibitors or rituximab employed in refractory cases. Overall disease-specific survival was 100% during the study period (median follow-up: 72.0 months); no mortality was directly attributable to IIM-related complications. Conclusions: Our study demonstrates that anti-MDA5 positive dermatomyositis in a Hungarian cohort is characterized by heterogeneous manifestations and a significant association between anti-Ro52 and ILD. The observed dissociation between low CK/CRP and elevated LDH underscores the necessity for a high index of suspicion, with LDH serving as a superior marker for disease activity. While ILD presents a significant risk, early and intensive multi-modal intervention may yield superior survival outcomes in European patients compared to the historical mortality rates reported in Asian cohorts. Full article

(This article belongs to the Special Issue Pathogenesis, Diagnostics, and Therapeutics for Rheumatic Diseases (2nd Edition))

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1 pages, 123 KB

Open AccessCorrection

Correction: Xiang et al. Preoperative Differentiation of Non-Subungual Glomus Tumors from Other Superficial Soft Tissue Tumors Using a Clinical and Ultrasound-Based Model. Biomedicines 2025, 13, 2883

by Hongjin Xiang, Qing Dan, Yue Zhai, Anran Guo, Yuzhou Shen, Run Wang, Desheng Sun and Xiangmei Chen

Biomedicines 2026, 14(3), 708; https://doi.org/10.3390/biomedicines14030708 - 19 Mar 2026

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Abstract

Error in Affiliation(s) [...] Full article

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

35 pages, 962 KB

Open AccessReview

A Review of Gut Microbiota Dynamics: From Healthy Gestation to Gestational Diabetes in Human and Mouse Models

by Dat Da Ly, Bryony A. McNeill, Kathryn Aston-Mourney and Leni R. Rivera

Biomedicines 2026, 14(3), 707; https://doi.org/10.3390/biomedicines14030707 - 18 Mar 2026

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Abstract

Over the past decades, gut microbiota has emerged as a critical modulator of human health and disease. Pregnancy involves substantial microbiota remodelling that influences offspring development, yet mechanisms linking maternal microbiota changes to gestational diabetes mellitus (GDM) remain unclear. The current literature lacks [...] Read more.

Over the past decades, gut microbiota has emerged as a critical modulator of human health and disease. Pregnancy involves substantial microbiota remodelling that influences offspring development, yet mechanisms linking maternal microbiota changes to gestational diabetes mellitus (GDM) remain unclear. The current literature lacks a comprehensive synthesis of pregnancy microbiota dynamics across healthy gestation to GDM, comparative human–murine analysis, and pregnancy-specific mechanistic frameworks distinct from type 2 diabetes models. This narrative review comprehensively synthesised evidence on gut microbiota composition in healthy pregnancy and GDM (2005–2025, NCBI PubMed) to identify convergent signatures and articulate pregnancy-specific mechanisms. Early pregnancy microbiota resembles non-pregnant individuals, whereas late pregnancy exhibits increased lactic acid-producing bacteria and reduced Firmicutes-to-Bacteroidetes (F/B) ratios. GDM exhibits pathological dysbiosis with elevated F/B ratios and reduced Bifidobacterium. Critically, GDM butyrate-producer patterns diverge from type 2 diabetes, suggesting pregnancy-specific mechanisms beyond glucose homeostasis. Despite these insights, methodological heterogeneity and cross-sectional designs constrain definitive conclusions. Longitudinal studies with standardised sequencing are essential to confirm consistent signatures and enable rational design of microbiota-modulating interventions (prebiotics, probiotics, synbiotics, postbiotics, diet) to optimise maternal health, prevent GDM, and support offspring development. Full article

(This article belongs to the Special Issue Advanced Research of Gut Microbiota in Health and Diseases—2nd Edition)

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