Biomedicines

23 pages, 3725 KB

Open AccessArticle

RXR Agonist V-125 Induces Distinct Transcriptional and Immunomodulatory Programs in Mammary Tumors of MMTV-Neu Mice Compared to Bexarotene

by Afrin Sultana Chowdhury, Lyndsey A. Reich, Karen T. Liby, Elizabeth S. Yeh and Ana S. Leal

Biomedicines 2026, 14(1), 80; https://doi.org/10.3390/biomedicines14010080 (registering DOI) - 30 Dec 2025

Abstract

Background: The retinoid X receptor (RXR) is a ligand-activated nuclear receptor that heterodimerizes with numerous partners to regulate diverse transcriptional programs. RXR agonists, including the FDA-approved drug bexarotene, show anti-tumor activity but are limited by adverse side effects. V-125 is a next-generation RXR [...] Read more.

Background: The retinoid X receptor (RXR) is a ligand-activated nuclear receptor that heterodimerizes with numerous partners to regulate diverse transcriptional programs. RXR agonists, including the FDA-approved drug bexarotene, show anti-tumor activity but are limited by adverse side effects. V-125 is a next-generation RXR agonist engineered for improved selectivity, pharmacokinetics, and reduced lipogenic effects. This study compares the molecular and functional effects of V-125 and bexarotene in HER2⁺ breast cancer models. Methods: Female MMTV-Neu mice bearing mammary tumors were treated with control, V-125 (100 mg/kg diet), or bexarotene (100 mg/kg diet) for 10 days. RNA sequencing was used to identify differentially expressed genes and pathways. Candidate targets were validated by qPCR and immunohistochemistry (IHC). Immune modulation was evaluated by IHC staining for CD8 cells and CD206⁺ macrophages in tumors to capture the tumor microenvironment. Functional assays in JIMT-1 human HER2⁺ cells assessed RXR target activation and clonogenic potential in tumor cells. Results: V-125 induced broader transcriptional changes than bexarotene, including selective upregulation of Nrg1, Nfasc, Lrrc26, and Chi3l1 genes associated with improved patient survival. Pathway analysis revealed regulation of immune activation, cancer signaling, and lipid metabolism. Both V-125 and bexarotene suppressed colony formation in JIMT-1 cells, confirming previous observations about RXR-dependent inhibition of tumor cell growth. Moreover, V-125 in vivo had distinct capabilities to increase CD8 cell infiltration and reduced CD206⁺ macrophages, whereas bexarotene did not. Conclusions: V-125 but not bexarotene reprograms tumor transcriptional programs and the immune landscape in an anti-tumor manner in the MMTV-neu mouse model and in in vitro models of HER2⁺ breast cancer. This highlights its promise as a selective RXR agonist with anti-tumor and immunomodulatory activity in HER2⁺ breast cancer. Full article

(This article belongs to the Special Issue Breast Cancer: New Diagnostic and Therapeutic Approaches)

► Show Figures

Graphical abstract

12 pages, 1452 KB

Open AccessArticle

Immunohistochemical Evaluation of ALDH1 and Maspin in Oral Potentially Malignant Disorders and Oral Carcinoma

by Bianca-Andreea Onofrei, Delia Gabriela Ciobanu Apostol, Mădălina-Gabriela Tanasă, Elena-Raluca Baciu, Cristina Popa, Ana Maria Sciuca, George Alexandru Maftei and Victor-Vlad Costan

Biomedicines 2026, 14(1), 79; https://doi.org/10.3390/biomedicines14010079 (registering DOI) - 30 Dec 2025

Abstract

Background/Objectives: Oral potentially malignant disorders (OPMDs), including oral leukoplakia (OLK), oral lichen planus (OLP), and actinic cheilitis (AC), have varying risks of progression to oral squamous cell carcinoma (OSCC). Biomarkers such as aldehyde dehydrogenase 1 (ALDH1) and mammary serine protease inhibitor (Maspin) [...] Read more.

Background/Objectives: Oral potentially malignant disorders (OPMDs), including oral leukoplakia (OLK), oral lichen planus (OLP), and actinic cheilitis (AC), have varying risks of progression to oral squamous cell carcinoma (OSCC). Biomarkers such as aldehyde dehydrogenase 1 (ALDH1) and mammary serine protease inhibitor (Maspin) have shown potential for diagnostic and prognostic use in oral cancer. The present study aimed to evaluate the immunoexpression of aldehyde dehydrogenase 1, a cancer stem cell marker associated with aggressiveness, and the mammary serine protease inhibitor, a potential tumor suppressor, in OPMD and OSCC tissues. Methods: A retrospective analysis was performed on 145 biopsy specimens collected from January 2015 to January 2023, including normal epithelium, OPMDs (OLK, OLP, AC), and OSCC. ALDH1 and Maspin expression levels were evaluated using immunohistochemistry, considering both the percentage of positive cells and staining intensity. Statistical analyses were carried out using the Statistical Package for the Social Sciences (SPSS, version 29.0; IBM Corp., Chicago, IL, USA). Results: Normal oral epithelium showed no expression of ALDH1, whereas 40.6% of OPMDs and 44.4% of OSCC samples exhibited high cytoplasmic ALDH1 expression. Nuclear ALDH1 expression was elevated in 29.7% of OPMDs and 38.9% of OSCCs (p < 0.001). Nuclear Maspin expression was high in 95.2% of normal tissues, in 67.2% of OPMDs and in 55.6% of OSCCs (p < 0.001). Maspin showed strong nuclear and cytoplasmic expression in normal tissue, but its expression decreased in OPMDs and OSCCs, with statistically significant reductions in both compartments (p < 0.001). Conclusions: The results indicate that ALDH1 upregulation and Maspin downregulation are hallmark events in oral carcinogenesis. Their combined evaluation provides a powerful tool for assessing dysplastic severity and malignant transformation risk in OPMDs. Future studies on larger cohorts are needed to confirm the prognostic utility of this dual-marker model. Full article

(This article belongs to the Special Issue Inflammatory Mechanisms, Biomarkers and Treatment in Oral Diseases)

22 pages, 13539 KB

Open AccessArticle

Trained Immunity in Bladder ILC3s Enhances Mucosal Defense Against Recurrent Urinary Tract Infections

by Qiaoqiao Pei, Jiaqi Liu, Ziwen Tang, Jiaqing Tan, Xu Han, Xinrong Hu, Zhou Liang, Feng Li, Changjian Zhu, Ruoni Lin, Ruilin Zheng, Jiani Shen, Qinghua Liu, Haiping Mao, Kefei Wu, Wei Chen and Yi Zhou

Biomedicines 2026, 14(1), 78; https://doi.org/10.3390/biomedicines14010078 (registering DOI) - 30 Dec 2025

Abstract

Background: Urinary tract infections (UTIs) rank among the most prevalent infectious diseases globally, with recurrent UTIs (rUTIs) posing substantial therapeutic challenges due to the lack of durable protective immunity. While trained immunity augments innate immune responses, its induction and functional significance in [...] Read more.

Background: Urinary tract infections (UTIs) rank among the most prevalent infectious diseases globally, with recurrent UTIs (rUTIs) posing substantial therapeutic challenges due to the lack of durable protective immunity. While trained immunity augments innate immune responses, its induction and functional significance in bladder-resident group 3 innate lymphoid cells (ILC3s) remain unknown. This study investigates whether ILC3s develop trained immunity following uropathogenic Escherichia coli (UPEC) exposure and how they contribute to mucosal defense against rUTIs. Methods: The ILC3 counts were detected in bladder sections from UTI patients and health controls (HC). A recurrent UTI mouse model was established through primary and secondary urethral UPEC inoculation. Bacterial loads in tissues were assessed, and single-cell suspensions were analyzed via flow cytometry. Bladder naïve- and UPEC-trained ILC3s were adoptively transferred, with evaluations of histopathology, epithelial barrier function, inflammation, and antimicrobial peptides. The in vitro ILC3 cell line MNK-3 was detected for IL-17A and IL-22 production following primary and secondary UPEC lysate stimulation. Results: We demonstrate that primary UPEC infection triggers ILC3 expansion in both human and murine bladders. Upon secondary challenge, these ILC3s develop trained immunity, characterized by enhanced proliferation, amplified IL-17A and IL-22 production, and improved pathogen clearance. Mechanistically, trained ILC3s reinforce urothelial barrier integrity through upregulation of antimicrobial peptides (Reg3b/Reg3g) and attenuate inflammatory pathology by suppressing pro-inflammatory cytokines (IL-6, TNF-α). Conclusions: We uncover an endogenous defense mechanism wherein UPEC primes bladder ILC3s via trained immunity, enabling amplified IL-17A- and IL-22-mediated protection against recurrent infections. These findings establish ILC3-trained immunity as a novel conceptual foundation, providing a basis for developing immunotherapies against rUTIs. Full article

(This article belongs to the Special Issue Advances in Pathogenesis and Treatment of Infectious Diseases)

► Show Figures

Figure 1

14 pages, 1021 KB

Open AccessArticle

Nasal Cytology Is Useful for Evaluating and Monitoring the Therapeutic Response to Biologics in Chronic Rhinosinusitis with Nasal Polyposis

by Gioia Piatti, Ludovica Battilocchi, Anna Cozzi, Lorenzo Maria Gaini, Mirko Aldè, Lorenzo Pignataro and Sara Torretta

Biomedicines 2026, 14(1), 77; https://doi.org/10.3390/biomedicines14010077 (registering DOI) - 30 Dec 2025

Abstract

Background/Objectives: In recent years, the recognition that type 2 inflammation plays a leading role in CRSwNP has enabled the more tailored treatment of the disease through improved patient endotyping. We studied 45 patients with severe CRSwNP who were treated with dupilumab or [...] Read more.

Background/Objectives: In recent years, the recognition that type 2 inflammation plays a leading role in CRSwNP has enabled the more tailored treatment of the disease through improved patient endotyping. We studied 45 patients with severe CRSwNP who were treated with dupilumab or mepolizumab. The aim was to evaluate the efficacy of these treatments on endoscopic, clinical and patient reported parameters, and to assess whether nasal cytology could be useful for identifying responsive patients and monitoring their response to biologic drugs. Methods: Follow-up visits were scheduled at baseline (T0), and at 3 (T3), 6 (T6), 12 (T12), and 24 months (T24). At each visit, patients underwent blood analysis, nasal endoscopy, and nasal scraping for cytology. They also completed the SNOT-22 questionnaire, a visual analog scale (VAS) for nasal obstruction and smell perception, and the Asthma Control Test (ACT) test in cases of concomitant asthma. Results: Biological therapy demonstrated broad efficacy in disease management, based on both clinical and cytological findings. The Nasal Polyp Score, SNOT-22 questionnaire, VAS scores for nasal obstruction and smell, and ACT score showed progressive improvement. Blood eosinophil counts and total IgE levels also decreased over time (T0 vs. T24: p = 0.008 and p < 0.001, respectively). At nasal cytology, a reduction in eosinophil cell count and in the mixed mast cell–eosinophil pattern during treatment with both biologics were observed (T0 vs. T24: p < 0.001). Positive effects were typically recorded within six months of treatment and were sustained after two years. Conclusions: Although the histological evaluation of infiltrated tissues remains the gold standard for assessing mucosal eosinophilia, nasal cytology appears to be a simpler, non-invasive, and repeatable method for evaluating local eosinophilia. Identifying endotypes and assessing the severity of inflammation are crucial for predicting the efficacy of different treatment options. Full article

(This article belongs to the Special Issue Targeted Biologic Therapies for Allergic Conditions: From Bench to Bedside)

► Show Figures

Figure 1

18 pages, 11888 KB

Open AccessArticle

Genetic Engineering of Umbilical Cord-Derived Mesenchymal Stem Cells to Enhance BMP-2 Secretion via Signal Peptide Optimization

by Nuzli Fahdia Mazfufah, Ismail Hadisoebroto Dilogo, Retno Wahyu Nurhayati, Delvac Oceandy, Silvia Tri Widyaningtyas, Maulana Dias Pratama and Goo Jang

Biomedicines 2026, 14(1), 76; https://doi.org/10.3390/biomedicines14010076 (registering DOI) - 30 Dec 2025

Abstract

Background/Objectives: Mesenchymal stem cells (MSCs) are recognized for their therapeutic potential due to their ability to secrete bioactive molecules. Among these secreted factors, bone morphogenetic protein-2 (BMP-2) is known as a secreted factor that plays a crucial role in bone healing and [...] Read more.

Background/Objectives: Mesenchymal stem cells (MSCs) are recognized for their therapeutic potential due to their ability to secrete bioactive molecules. Among these secreted factors, bone morphogenetic protein-2 (BMP-2) is known as a secreted factor that plays a crucial role in bone healing and regeneration. However, MSCs naturally secrete only small amounts of BMP-2. To improve the bone healing capacity of MSCs, it is essential to enhance the secretion of BMP-2 in MSCs. One approach that can be used to achieve this goal is by genetically engineering MSCs. Incorporating signal peptides (SPs) into the inserted gene sequence can significantly improve protein secretion efficiency. In this proof-of-concept study, we explored the role of SPs in optimizing BMP-2 secretion in umbilical cord-derived MSCs; Methods: Three human-derived SPs, namely glial-derived neurotrophic factor (GDNF), chemotactic antibacterial glycoprotein 7 (CAP7), and platelet-derived growth factor subunit B (PDGFB), were selected. Transfection of MSCs was performed using polyethylenimine, Lipofectamine 2000^®, and Lipofectamine 3000^®. Transfection efficiency confirmed based on Green Fluorescence Protein expression. BMP-2 secretion levels were quantified using an ELISA assay; Results: Lipofectamine 3000^® achieved the highest transfection efficiency, reaching approximately 10%. BMP-2 secretion levels varied significantly depending on the SPs used, with PDGFB yielding the highest BMP-2 concentration (279.21 ± 6.91 pg/mL), followed by GDNF (265.65 ± 11.49 pg/mL) and CAP7 (233.72 ± 32.33 pg/mL); Conclusions: These findings demonstrate that SP selection critically influences BMP-2 secretion efficiency in genetically engineered MSCs and underscore its potential to enhance the therapeutic applicability of MSC-based strategies for bone healing. Full article

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

► Show Figures

Figure 1

16 pages, 871 KB

Open AccessArticle

Long-Term Prognosis and Impact Factors of Metoprolol Treatment in Children with Vasovagal Syncope

by Jing Wang, Ping Liu, Yuli Wang, Junbao Du, Ying Liao and Hongfang Jin

Biomedicines 2026, 14(1), 75; https://doi.org/10.3390/biomedicines14010075 (registering DOI) - 30 Dec 2025

Abstract

Objective: To investigate long-term prognosis and impact factors in children with vasovagal syncope (VVS) receiving metoprolol therapy. Method: This retrospective study included children with VVS who underwent metoprolol therapy at the Pediatric Syncope Unit of Peking University First Hospital between January 2012 and [...] Read more.

Objective: To investigate long-term prognosis and impact factors in children with vasovagal syncope (VVS) receiving metoprolol therapy. Method: This retrospective study included children with VVS who underwent metoprolol therapy at the Pediatric Syncope Unit of Peking University First Hospital between January 2012 and November 2023. Baseline demographic data, pre-treatment indices, including head-up tilt test (HUTT) and 24 h Holter monitoring, were collected. All participants received standardized metoprolol therapy for a minimum duration of one month. Follow-up was conducted between June and July 2025, with syncope recurrence as the primary endpoint. Multivariable Cox proportional hazards regression analysis was performed to identify independent impact factors of prognosis and to construct a Prognostic Risk Score (PRS) model. The model’s performance was rigorously validated through receiver operating characteristic (ROC) curve analysis, decision curve analysis (DCA), and Bootstrap resampling (1000 iterations). Furthermore, children were stratified into high- and low-risk groups based on median PRS values. Kaplan–Meier survival analysis was then performed to assess the model’s discriminative efficacy. Result: This study included 97 children diagnosed with VVS. The median duration of metoprolol therapy was 2.5 months (interquartile range [IQR]: 2.0–3.0 months), with a median follow-up period of 59 months (IQR: 25.5–72 months). During follow-up, syncope recurrence was observed in 37 patients, while 60 patients remained symptom-free. COX regression analysis showed that time-domain indices of heart rate variability (HRV), including the standard deviation of all NN intervals (SDNN) and the triangular index (TR), as well as the frequency-domain index of HRV very low frequency (VLF), were relative factors of the long-term prognosis in children with VVS treated with metoprolol. Based on the above three identified factors, the PRS model was calculated as: PRS = 0.03 × SDNN − 0.02 × VLF − 0.1 × TR. ROC showed that the area under the curve (AUC) for discriminative power related to long-term prognosis was 0.808 (p < 0.01). The cumulative recurrence rate of symptoms in the high-risk score group was significantly higher than that in the low-risk score group (p < 0.01). The DCA curve demonstrated the clinical applicability of the model. Bootstrap internal verification indicated high stability, with the bias-corrected and accelerated (Bca) confidence interval (CI) of the C index ranging from 0.71 to 0.89. Conclusions: After metoprolol treatment, 38.1% of children with VVS experienced syncope recurrence during a median follow-up period of 59 months. Baseline HRV index, SDNN, TR, and VLF were identified as factors associated with the long-term prognosis of children with VVS treated with metoprolol. The PRS model based on the above indices demonstrated good value in linking to the individual long-term prognosis. Full article

(This article belongs to the Special Issue Cardiovascular Diseases: From Pathophysiology to Novel Therapeutic Approaches)

► Show Figures

Graphical abstract

15 pages, 717 KB

Open AccessSystematic Review

Enhanced Monovision Intraocular Lenses: Current Status and Future Perspectives—Systematic Review

by Zofia Honorata Trusiak, Aleksandra Leoniuk, Aleksandra Tomaszuk, Michał Sawicki and Joanna Konopińska

Biomedicines 2026, 14(1), 74; https://doi.org/10.3390/biomedicines14010074 (registering DOI) - 29 Dec 2025

Abstract

Background/Objectives: Cataract is the most common cause of blindness in the world. Enhanced monovision intraocular lenses (EMV IOLs) have been recently made available on the market. In this study, we aimed to further the understanding of EMV IOLs and their potential benefits [...] Read more.

Background/Objectives: Cataract is the most common cause of blindness in the world. Enhanced monovision intraocular lenses (EMV IOLs) have been recently made available on the market. In this study, we aimed to further the understanding of EMV IOLs and their potential benefits in cataract surgery, while also identifying areas for future research. Methods: In this review, we discuss the findings of a few previously published comparative studies concerning different types of EMV IOLs. We conducted a systematic review of comparative studies (randomized controlled trials, prospective and retrospective observational studies) describing binocular uncorrected intermediate vision acuity (UIVA) in patients after cataract surgery and implantation of monofocal plus IOLs based on emmetropia and monovision. Results: The secondary outcomes measured were uncorrected distance visual acuity, uncorrected near visual acuity (UNVA; described in eight studies), spectacle independence and patients’ satisfaction. A total of 199 patients (average age 68.11 years) were analyzed in the included studies; of these patients, 169 achieved UNVA reaching an average of 0.188 logMAR. Conclusions: The monovision approach may provide enhanced intermediate and near vision without significantly compromising distance vision or patient satisfaction, though results varied across studies. Future randomized trials with standardized outcome measures and conducted over a longer follow-up period are warranted to confirm these findings. Full article

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

33 pages, 1431 KB

Open AccessReview

Microbiota-Driven Immune Dysregulation Along the Gut–Lung–Vascular Axis in Asthma and Atherosclerosis

by Elena-Larisa Zimbru, Răzvan-Ionuț Zimbru, Florina-Maria Bojin, Sorin Dan Chiriac, Laura Haidar, Minodora Andor, Gabriela Tănasie, Carmen Tatu, Marius Georgescu, Cristina Uța, Camelia-Felicia Bănărescu, Sabine Groza and Carmen Panaitescu

Biomedicines 2026, 14(1), 73; https://doi.org/10.3390/biomedicines14010073 (registering DOI) - 29 Dec 2025

Abstract

Background: Asthma and atherosclerosis frequently coexist in clinical populations and share convergent immunometabolic pathways amplified by gut microbial dysbiosis. We propose the gut–lung–vascular axis as a unifying mechanistic framework connecting epithelial and endothelial inflammation providing a foundation for understanding shared inflammatory mechanisms beyond [...] Read more.

Background: Asthma and atherosclerosis frequently coexist in clinical populations and share convergent immunometabolic pathways amplified by gut microbial dysbiosis. We propose the gut–lung–vascular axis as a unifying mechanistic framework connecting epithelial and endothelial inflammation providing a foundation for understanding shared inflammatory mechanisms beyond tissue-specific disease boundaries. Methods: A targeted narrative review systematically appraised clinical, experimental and multi-omics studies published over the last five years to delineate microbiota-driven pathways relevant to asthma and atherosclerosis. Particular emphasis was placed on specific microbial taxa, metabolite profiles and immunometabolic networks that connect gut dysbiosis with respiratory and cardiovascular dysfunction. Results: Across human and experimental cohorts, dysbiosis marked by depletion of short-chain fatty acids (SCFAs) producing taxa (Faecalibacterium, Roseburia, Bacteroides) and enrichment of pathobionts (Proteobacteria, Haemophilus, Moraxella, Streptococcus) promotes epithelial and endothelial barrier dysfunction, amplifying Th2/Th17-skewed inflammation and endothelial injury. Key metabolites, including SCFAs, trimethylamine N-oxide (TMAO), secondary bile acids (BA), indole/tryptophan derivatives and lipopolysaccharides (LPS), serve as molecular connectors linking gut, airway and vascular inflammation. Microbial signatures and metabolomic patterns hold emerging diagnostic and therapeutic potential, and several drug classes (e.g., statins, corticosteroids, proton-pump inhibitors (PPIs)) further modulate host–microbiota interactions. Conclusions: Shared microbial taxa and metabolite signatures in asthma and atherosclerosis support microbiota-mediated immune dysregulation along the gut–lung–vascular axis as a common pathogenic framework. Microbial and metabolite profiling may enable improved risk stratification and precise, microbiota-targeted therapies. Integrating microbiome-informed diagnostics and personalized interventions could help reduce systemic inflammation and the burden of these overlapping inflammatory diseases. Full article

(This article belongs to the Special Issue Omics Approaches on Immune-Mediated Inflammatory Diseases: Towards Novel Biomarkers and Potential Therapeutic Targets, 3rd Edition)

► Show Figures

Figure 1

30 pages, 1460 KB

Open AccessReview

Neuron–Glioma Synapses in Tumor Progression

by Cristina Cueto-Ureña, María Jesús Ramírez-Expósito and José Manuel Martínez-Martos

Biomedicines 2026, 14(1), 72; https://doi.org/10.3390/biomedicines14010072 (registering DOI) - 29 Dec 2025

Abstract

Gliomas are the most common malignant primary brain tumors in adults. The treatment of high-grade gliomas is very limited due to their diffuse infiltration, high plasticity, and resistance to conventional therapies. Although they were long considered passive massive lesions, they are now regarded [...] Read more.

Gliomas are the most common malignant primary brain tumors in adults. The treatment of high-grade gliomas is very limited due to their diffuse infiltration, high plasticity, and resistance to conventional therapies. Although they were long considered passive massive lesions, they are now regarded as functionally integrated components of neural circuits, as they form authentic electrochemical synapses with neurons. This allows them to mimic neuronal activity to drive tumor growth and invasion. Ultrastructural studies show presynaptic vesicles in neurons and postsynaptic densities in glioma cell membranes, while electrophysiological recordings detect postsynaptic currents in tumor cells. Tumor microtubules (TMs), dynamic cytoplasmic protrusions enriched in AMPA receptors, are the structures responsible for glioma–glioma and glioma–neuron connectivity, also contributing to treatment resistance and tumor network integration. In these connections, neurons release glutamate that mainly activates their AMPA receptors in glioma cells, while gliomas release excess glutamate, causing excitotoxicity, altering the local excitatory-inhibitory balance, and promoting a hyperexcitable and pro-tumorigenic microenvironment. In addition, certain gliomas, such as diffuse midline gliomas, have altered chloride homeostasis, which makes GABAergic signaling depolarizing and growth promoting. Synaptogenic factors, such as neuroligin-3 and BDNF, further enhance glioma proliferation and synapse formation. These synaptic and paracrine interactions contribute to cognitive impairment, epileptogenesis, and resistance to surgical and pharmacological interventions. High functional connectivity within gliomas correlates with shorter patient survival. Therapies such as AMPA receptor antagonists (perampanel), glutamate release modulators (riluzole or sulfasalazine), and chloride cotransporter inhibitors (NKCC1 blockers) aim to improve outcomes for patients. Full article

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

► Show Figures

Figure 1

28 pages, 3347 KB

Open AccessArticle

Stability of Myeloid Cell Phenotype and Function Across a Broad Age Range in Humans and Cynomolgus Monkeys, and a Dominant Contribution of Humoral Factors in the Control of Bacterial Infection

by Elena V. Lysakova, Marina Y. Burak, Ilya Larin, Sergey A. Chuvpilo, Viktor S. Laktyushkin, Alexander N. Shumeev, Igor E. Pismennyi, Vladimir Y. Toshchakov, Mikhail Y. Bobrov and Stanislav A. Rybtsov

Biomedicines 2026, 14(1), 71; https://doi.org/10.3390/biomedicines14010071 (registering DOI) - 29 Dec 2025

Abstract

Background: Immune aging is a complex process involving various cellular changes, such as a myeloid bias, decreased functional activity of immune cells, accumulation of senescent cells, and alterations in serum levels of bactericidal humoral factors. As believed, these changes contribute to increased [...] Read more.

Background: Immune aging is a complex process involving various cellular changes, such as a myeloid bias, decreased functional activity of immune cells, accumulation of senescent cells, and alterations in serum levels of bactericidal humoral factors. As believed, these changes contribute to increased susceptibility of older adults to infectious diseases. Myeloid cells are considered the first line of defense against bacterial invasion. However, it remains unclear whether the protective functions of myeloid cells diminish in active older adults and whether potential age-related changes are evolutionarily conserved across primates. Methods: In this study, myeloid cell populations from peripheral blood and bone marrow of cynomolgus macaques and human peripheral blood were analyzed across a broad age range for phenotypic and functional characteristics, e.g., E. coli phagocytosis, secretion of proinflammatory factors, genetic instability, and signs of cellular aging. Results: Despite minor interspecies phenotypic differences in granulocyte populations, both the quantity and functions of myeloid cells were remarkably stable during aging in both species. Myeloid cells maintained genetic stability, and high SA-β-Gal activity was observed, likely reflecting metabolic traits rather than age-related changes. Importantly, a predominant and age-independent role of humoral factors, rather than cellular mechanisms, was identified in the initial control of bacterial infection. Conclusions: These findings suggest that innate immune functions remain stable for a long time during aging in both species. Full article

(This article belongs to the Section Immunology and Immunotherapy)

► Show Figures

Figure 1

3 pages, 146 KB

Open AccessEditorial

Reeling in a New Line on Zebrafish Research

by James A. Marrs

Biomedicines 2026, 14(1), 70; https://doi.org/10.3390/biomedicines14010070 (registering DOI) - 29 Dec 2025

Abstract

In this fourth volume of the Biomedicines Special Issue “Zebrafish Models for Development and Disease,” a great variety of advances and scientific syntheses arose from our casting around the vast zebrafish research stream [...] Full article

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

17 pages, 1369 KB

Open AccessReview

Coenzyme A in Brain Biology and Neurodegeneration

by Dejun Zhang, Charlie Brett, Jason Cho, Tammaryn Lashley and Ivan Gout

Biomedicines 2026, 14(1), 69; https://doi.org/10.3390/biomedicines14010069 (registering DOI) - 29 Dec 2025

Abstract

Coenzyme A (CoA) biology has been extensively studied in health and disease due to the central role of CoA in numerous metabolic and signalling processes. CoA is essential for all living organisms, and its biosynthesis and homeostasis are tightly regulated by nutrient availability, [...] Read more.

Coenzyme A (CoA) biology has been extensively studied in health and disease due to the central role of CoA in numerous metabolic and signalling processes. CoA is essential for all living organisms, and its biosynthesis and homeostasis are tightly regulated by nutrient availability, mitogenic stimuli, and stress signals. Disruptions in CoA biosynthesis, caused by inborn mutations in genes encoding enzymes of the CoA biosynthetic pathway (such as PANK2 and CoASy), lead to neurodegeneration, indicating the critical role of CoA/CoA thioesters in the function and viability of neuronal cells. The molecular mechanisms linking CoA deficiency to neurodegeneration remain unknown, but recent studies have highlighted the involvement of disrupted metabolism and redox homeostasis. The antioxidant function of CoA, mediated by protein CoAlation, has recently emerged as a novel and important mechanism of redox regulation. This review highlights well-established principles of CoA in neuronal metabolism and summarises recent advances in our understanding of its role in adaptive responses to oxidative and metabolic stress. The identification of enzymes involved in the CoAlation/deCoAlation cycle, together with the development of novel analytical tools and methodologies, may provide new insights into the discovery of more effective diagnostic and therapeutic approaches for targeting neurodegenerative diseases. Full article

(This article belongs to the Special Issue Mechanisms and Novel Therapeutic Approaches for Neurodegenerative Diseases (3rd Edition))

► Show Figures

Figure 1

6 pages, 179 KB

Open AccessEditorial

From Molecules to Medicine: Deciphering Obesity and Lipid Metabolism for Translational Insights

by Sandeep Kumar and Abhishek Gupta

Biomedicines 2026, 14(1), 68; https://doi.org/10.3390/biomedicines14010068 (registering DOI) - 29 Dec 2025

Abstract

Obesity, type 2 diabetes (T2D), and insulin resistance are pervasive metabolic disorders marked by chronic low-grade inflammation and systemic metabolic disorders. The emerging field of immunometabolism highlights how interactions between immune processes and metabolic pathways in adipose tissue, liver, muscle, and pancreatic islets [...] Read more.

Obesity, type 2 diabetes (T2D), and insulin resistance are pervasive metabolic disorders marked by chronic low-grade inflammation and systemic metabolic disorders. The emerging field of immunometabolism highlights how interactions between immune processes and metabolic pathways in adipose tissue, liver, muscle, and pancreatic islets contribute to disease pathogenesis. Lipid dysregulation plays a central role in these processes, with distinct lipid molecules identified in obese patients as compared to lean patients that correlate with insulin resistance, inflammation, and vascular dysfunction. This Special Issue compiles a multidisciplinary body of research aimed at elucidating molecular mechanisms, identifying novel biomarkers, and exploring innovative therapeutic strategies. Key contributions include studies on omega-3 long-chain polyunsaturated fatty acids (LCPUFAs) and their differential associations with neurocognitive development; the potential of beta-defensin 2 as a biomarker linking gut-derived inflammation and metabolic dysfunction; and the promotion of adipocyte browning by Carnosic acid via AMPK activation and GSK3β inhibition. Additionally, reviews of phytochemicals underscore their multisystem therapeutic potential, while investigations into sodium–glucose cotransporter-2 (SGLT2) inhibitors suggest possible metabolic and neuroprotective benefits beyond glucose control. Maternal lipid metabolism during pregnancy and its impact on maternal fetal health further emphasize the clinical complexity of lipid dysregulation. Despite promising insights, significant gaps remain regarding causality versus correlation in lipid biomarkers, standardization of analytical methodologies, tissue heterogeneity, and unintended effects of metabolic interventions. Collectively, these studies underscore the necessity of integrative, mechanism-driven research to bridge fundamental biology with translational and clinical applications, ultimately advancing precision therapies for metabolic diseases. Full article

(This article belongs to the Special Issue From Molecules to Medicine: Deciphering Obesity and Lipid Metabolism for Translational Insights)

4 pages, 155 KB

Open AccessEditorial

Recent Advances in Understanding of the Role of Synuclein Family Members in Health and Disease Volume II

by Natalia N. Ninkina and Vladimir L. Buchman

Biomedicines 2026, 14(1), 67; https://doi.org/10.3390/biomedicines14010067 - 29 Dec 2025

Abstract

The synuclein family of three short, intrinsically disordered and predominantly neurospecific proteins (α-, β-, and γ-synuclein) [...] Full article

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

15 pages, 1783 KB

Open AccessArticle

A Multikinase Inhibitor AX-0085 Blocks FGFR1 Activation to Overcomes Osimertinib Resistance in Non-Small Cell Lung Cancer

by Byung-Ho Rhie, Janardhan Keshav Karapurkar, Hyun-Yi Kim, Sang Hyeon Woo, D. A. Ayush Gowda, Dong Ha Kim, Myeong Jun Choi, Young Jun Park, Viswanathaiah Matam, Yoonki Hong, Seok-Ho Hong, Suresh Ramakrishna and Kye-Seong Kim

Biomedicines 2026, 14(1), 66; https://doi.org/10.3390/biomedicines14010066 - 28 Dec 2025

Abstract

Background: Osimertinib is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) with high efficacy in treating patients with advanced non-small cell lung cancer (NSCLC) harboring EGFR-activating mutations. Although osimertinib is a frontline anticancer agent for NSCLC, several patients inevitably develop [...] Read more.

Background: Osimertinib is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) with high efficacy in treating patients with advanced non-small cell lung cancer (NSCLC) harboring EGFR-activating mutations. Although osimertinib is a frontline anticancer agent for NSCLC, several patients inevitably develop tumor recurrence caused by osimertinib resistance. The activation of anexelekto (AXL) or fibroblast growth factor receptor 1 (FGFR1) is reported as a major factor driving osimertinib resistance in NSCLC. Thus, targeting AXL and FGFR1 offers the potential to overcome osimertinib resistance. Methods: In this study, we generated osimertinib-resistant cell lines from EGFR-mutant NSCLC cell lines in vitro and investigated the biological significance of AX-0085 on these cell lines by conducting transcriptomic analyses. Results: The expression of several genes associated with MAPK, ERK, and FGF receptor signaling pathways, including AXL, was altered upon AX-0085 treatment of osimertinib-resistant cells. Furthermore, AX-0085 treatment effectively blocked AXL and FGFR1 activation and sensitized osimertinib-resistant cells. Additionally, AX-0085 inhibited AXL and FGFR1-dependent oncogenic events, including cell proliferation, clonogenicity, and migration. Conclusions: The dual inhibition of AXL and FGFR1 by AX-0085 can overcome acquired osimertinib resistance, supporting its potential as a therapeutic strategy for treating patients with osimertinib-resistant tumors. Full article

(This article belongs to the Special Issue Advancements in Lung Cancer Precision Oncology Research and Treatments)

► Show Figures

Figure 1

9 pages, 2816 KB

Open AccessCommunication

Keratinocyte HIF-1α Orchestrates Imiquimod-Induced Psoriasiform Inflammation by Promoting Type 3 Inflammation

by Dohyeon Ku and Kwonik Oh

Biomedicines 2026, 14(1), 65; https://doi.org/10.3390/biomedicines14010065 - 28 Dec 2025

Abstract

Psoriasis is a chronic inflammatory skin disease driven by the IL-23/IL-17 axis and characterized by keratinocyte hyperproliferation, epidermal thickening, and immune infiltration. While immune cell-intrinsic roles of hypoxia-inducible factor-1α (HIF-1α) have been reported, the contribution of keratinocyte HIF-1α remains less clear. In this [...] Read more.

Psoriasis is a chronic inflammatory skin disease driven by the IL-23/IL-17 axis and characterized by keratinocyte hyperproliferation, epidermal thickening, and immune infiltration. While immune cell-intrinsic roles of hypoxia-inducible factor-1α (HIF-1α) have been reported, the contribution of keratinocyte HIF-1α remains less clear. In this study, we investigated epithelial HIF function in murine models of skin inflammation using keratinocyte-specific HIF-1α knockout (K14-Cre Hif1a^fl/fl) mice. HIF-1α deficiency attenuated epidermal hyperplasia and type 3 inflammation in the imiquimod (IMQ)-induced psoriasiform model but had little effect in DNFB-induce contact hypersensitivity and MC903-induced atopic dermatitis model. Flow cytometry of draining lymph nodes revealed reduced frequencies of inflammatory cells including IL-17-producing γδ T cells in HIF-1α-deficient mice. In IMQ-treated skin, HIF-1α deficiency led to reduced Il17, Il23 and neutrophil-attracting chemokine transcript levels and diminished Ly6G⁺ neutrophil infiltration. These findings identify keratinocyte HIF-1α as a central regulator of psoriasiform inflammation and suggest that epithelial HIF signaling could be a potential therapeutic target for psoriasis. Full article

(This article belongs to the Section Immunology and Immunotherapy)

► Show Figures

Figure 1

14 pages, 572 KB

Open AccessArticle

Postnatal Changes of Renin and Aldosterone in Term and Preterm Infants from Birth to Day 5

by Yukihito Imagawa, Yu Masuda, Yuki Nakata, Kentaro Fujitani, Aine Takahashi, Keisuke Shirai, Takumi Kido, Mariko Ashina, Kenji Tanimura, Kandai Nozu and Kazumichi Fujioka

Biomedicines 2026, 14(1), 64; https://doi.org/10.3390/biomedicines14010064 - 27 Dec 2025

Abstract

Background/Objectives: The renin–angiotensin–aldosterone system (RAAS) is pivotal for neonatal circulation and renal adaptation; however, postnatal changes in serum renin and aldosterone immediately after birth remain unclear. This study aimed to establish postnatal changes in these hormones at birth and over the first [...] Read more.

Background/Objectives: The renin–angiotensin–aldosterone system (RAAS) is pivotal for neonatal circulation and renal adaptation; however, postnatal changes in serum renin and aldosterone immediately after birth remain unclear. This study aimed to establish postnatal changes in these hormones at birth and over the first week of life. Methods: We retrospectively analyzed 374 neonates admitted to Kobe University Hospital between October 2020 and September 2023, with serum renin and aldosterone measured on days 0 and 5 of life. Exclusion criteria were multiple congenital anomalies, severe asphyxia, major peripartum hemorrhage, and in utero exposure to angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers. Hormone levels were compared between term and preterm infants, and correlations with gestational age were assessed. Results: Serum renin concentrations were higher on day 0 than on day 5 (median 99.9 pg/mL [2.6–773.3] vs. 19.9 pg/mL [0.6–2304], p < 0.0001), and aldosterone concentrations similarly decreased (714 pg/mL [6.9–6334] vs. 551 pg/mL [0–11,930], p < 0.0001). At birth, renin and aldosterone levels did not differ significantly between groups. By day 5, both renin (32.8 pg/mL [0.6–2304] vs. 14.5 pg/mL [0.6–208]) and aldosterone (689 pg/mL [4–11,930] vs. 471 pg/mL [13–4697]) concentrations were significantly higher in preterm than in term neonates (p < 0.0001). Conclusions: This study describes early postnatal changes in renin and aldosterone, with higher concentrations at birth than on day 5 and persistently elevated levels in preterm infants. These findings indicate increased RAAS activity in preterm neonates and suggest a greater vulnerability to fluid, electrolyte, and blood pressure instability during early life. Full article

(This article belongs to the Special Issue State-of-the-Art Neonatal Medicine in Japan)

► Show Figures

Figure 1

20 pages, 1567 KB

Open AccessArticle

Antioxidant and Neuroprotective Capacity of Resveratrol-Loaded Polymeric Micelles in In Vitro and In Vivo Models with Generated Oxidative Stress

by Maria Lazarova, Elina Tsvetanova, Almira Georgieva, Miroslava Stefanova, Krasimira Tasheva, Lyubomira Radeva, Magdalena Kondeva-Burdina and Krassimira Yoncheva

Biomedicines 2026, 14(1), 63; https://doi.org/10.3390/biomedicines14010063 - 27 Dec 2025

Abstract

Background: Resveratrol (3,5,4′-trihydroxy-trans-stilbene, RVT) is one of the most extensively studied natural polyphenols, with numerous health benefits documented in the literature. One of its most characterized biological properties is the strong antioxidant capacity. However, its poor biopharmaceutical properties limit its in vivo [...] Read more.

Background: Resveratrol (3,5,4′-trihydroxy-trans-stilbene, RVT) is one of the most extensively studied natural polyphenols, with numerous health benefits documented in the literature. One of its most characterized biological properties is the strong antioxidant capacity. However, its poor biopharmaceutical properties limit its in vivo applicability. In this study, we conducted a detailed comparative analysis of the antioxidant and protective capacity of pure and loaded into Pluronic micelles resveratrol. Methods: Various in vitro antioxidant assays, such as DPPH, ABTS, superoxide anion radical scavenging, ferric (FRAP), and copper-reducing power assay (CUPPRAC), and iron-induced lipid peroxidation were performed. In addition, the in vitro 6-OHDA model of neurotoxicity in brain synaptosomes and the in vivo scopolamine (Sco)-induced model of cognitive impairment in rats were also employed. The main antioxidant biomarkers—the levels of lipid peroxidation (LPO) and total glutathione (GSH), as well as activities of superoxide dismutase, catalase, and glutathione peroxidase—were measured in the cortex and hippocampus. Results: The results from the in vitro tests demonstrated better ferric-reducing power activity and better neuroprotective capacity of the micellar resveratrol (mRVT), as evidenced by preserved synaptosomal viability and maintained GSH levels in a concentration-dependent manner in 6-OHDA-induced neurotoxicity. Regarding the in vivo results, mRVT (10 µM concentration) was the most effective treatment in supporting recognition memory formation in dementia rats. Further, mRVT demonstrated better LPO protective capacity in the hippocampus and GSH preserving activity in the cortex than the pure drug. Conclusions: The incorporation of resveratrol in polymeric micelles could enhance its antioxidant and neuroprotective effects. Full article

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

► Show Figures

Figure 1

13 pages, 777 KB

Open AccessArticle

Predicting Hypocalcemia and Identifying Supplementation Needs After Total Thyroidectomy: The Role of Perioperative PTH Measurements

by Angeliki Emmanouilidou, Athina Stamati, Eleni Avramidou, Philippos Tasioudis, Eleni Tziona, Charilaos Koulouris, Michael Karanikas, Kalliopi Pazaitou-Panayiotou and Nickos Michalopoulos

Biomedicines 2026, 14(1), 62; https://doi.org/10.3390/biomedicines14010062 - 26 Dec 2025

Abstract

Background: Post-thyroidectomy hypocalcemia is a common complication, yet the optimal perioperative markers for identifying high-risk patients and guiding supplementation remain debated. This study aimed to evaluate factors associated with hypocalcemia at 24 h after total thyroidectomy, identify independent predictors, and assess the [...] Read more.

Background: Post-thyroidectomy hypocalcemia is a common complication, yet the optimal perioperative markers for identifying high-risk patients and guiding supplementation remain debated. This study aimed to evaluate factors associated with hypocalcemia at 24 h after total thyroidectomy, identify independent predictors, and assess the reliability of early PTH measurement in determining supplementation needs. Methods: We conducted a single-center prospective cohort study including 200 patients undergoing total thyroidectomy at Genesis Hospital, Thessaloniki, between November 2022 and March 2025. PTH was measured preoperatively, 10 min post-resection, and at 24 and 72 h; calcium and phosphorus were measured preoperatively and postoperatively. Results: Independent predictors of hypocalcemia at 24 h were female sex, preoperative calcium, and PTH at 10 min. Age, pathology, incidental parathyroid excision, and extent of surgery were not significantly associated with hypocalcemia. ROC analysis showed that a preoperative calcium cutoff of 9.47 mg/dL yielded an AUC of 0.73, with 70.1% sensitivity and an NPV of 82%. PTH at 10 min with a cutoff of 24.6 pg/mL yielded an AUC of 0.66, with 70.1% sensitivity and an NPV of 79%. For supplementation needs, PTH at 10 min demonstrated excellent discrimination, with a cutoff of 16.3 pg/mL at 24 h and 14.1 pg/mL at 72 h. Conclusions: Preoperative calcium and PTH measured 10 min after thyroid removal are useful markers for predicting hypocalcemia after total thyroidectomy, with early PTH also accurately identifying supplementation needs. Full article

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

► Show Figures

Figure 1

Journal Description

Biomedicines

Latest Articles

Journal Menu

Journal Browser

Highly Accessed Articles

Latest Books

E-Mail Alert

News

Topics

Conferences

Special Issues

Topical Collections

Further Information

Guidelines

MDPI Initiatives

Follow MDPI