Biomedicines

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)

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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)

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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)

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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))

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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, 1897 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)

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)

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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)

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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)

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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)

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13 pages, 947 KB

Open AccessArticle

Intrauterine Administration of PBMC Modulated with IFN-τ Before Embryo Transfer Improves Clinical Outcomes of IVF Patients—A Randomized Control Trial

by Margarita Ruseva, Dimitar Parvanov, Rumiana Ganeva, Maria Handzhiyska, Jinahn Safir, Stefka Nikolova, Teodora Tihomirova, Dimitar Metodiev, Georgi Stamenov and Savina Hadjidekova

Biomedicines 2026, 14(1), 61; https://doi.org/10.3390/biomedicines14010061 - 26 Dec 2025

Abstract

Objective: The aim of this study was to evaluate whether intrauterine administration of autologous peripheral blood mononuclear cells (PBMCs) activated with interferon tau (IFN-τ) before embryo transfer improves implantation and pregnancy outcomes in IVF patients. Methods: This single-center, prospective, randomized, controlled trial was [...] Read more.

Objective: The aim of this study was to evaluate whether intrauterine administration of autologous peripheral blood mononuclear cells (PBMCs) activated with interferon tau (IFN-τ) before embryo transfer improves implantation and pregnancy outcomes in IVF patients. Methods: This single-center, prospective, randomized, controlled trial was conducted at Nadezhda Women’s Health Hospital (Approval No.: 6/28022023). The study was registered at ClinicalTrials.gov (NCT05775198). Randomization was computer-generated with allocation concealed via sealed envelopes. Participants and statisticians were blinded to group assignment; clinicians were not. Women aged 21–50 undergoing frozen–thawed embryo transfer with euploid embryos were included. Exclusion criteria included uterine anomalies, autoimmune, oncologic conditions, infections, or use of immunosuppressants. Participants (n = 340) were randomized 1:1 to receive either intrauterine infusion of autologous PBMCs activated in vitro with IFN-τ or standard IVF care without PBMC treatment. PBMCs were cultured with recombinant IFN-τ, washed, and infused 24 h prior to single euploid blastocyst transfer. A total of 14 patients were excluded from analysis because of early dropout, leaving 326 (n = 167; n = 159) patients for modified intention-to-treat analysis. Primary outcomes included implantation rate (elevated urinary or blood hCG), clinical pregnancy (fetal heartbeat at 6–8 weeks), and live birth rates. Miscarriage rate and safety were secondary objectives. Patients were followed up until 6 weeks post pregnancy resolution. Results: In the intervention group, 38.3% of patients achieved implantation, compared to 27.7% in the controls (OR 1.6, 95% CI: 1.0–2.6, p = 0.04). Live birth rates were also significantly higher in the IFN-τ-modulated PBMC group (28.7% vs. 17.6%, OR 1.9, 95% CI: 1.1–3.2; p = 0.02). While the clinical pregnancy rate was higher, it did not reach statistical significance (34.7% vs. 25.8%, p = 0.08). There was no difference between the groups in terms of miscarriage (p = 0.4). No serious adverse events were reported after treatment, during pregnancy or in the postnatal period. Conclusions: Intrauterine treatment with IFN-τ-activated PBMCs before ET significantly improves implantation and live birth rates in IVF patients. Full article

(This article belongs to the Special Issue Advances in Medically Assisted Reproduction)

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19 pages, 674 KB

Open AccessArticle

The TRPV1 Channel Modulator Imidazo[1,2-a]Indole Derivative Exhibits Pronounced and Versatile Anti-Inflammatory Activity In Vivo

by Pavel A. Galenko-Yaroshevsky, Anait V. Zelenskaya, Konstantin F. Suzdalev, Tatyana N. Popova, Aleksandra N. Kvetkina, Margarita M. Shamatova, Elena N. Chuyan, Marina Yu. Ravaeva, Roman A. Murashko, Tereza R. Glechyan, Alina V. Sergeeva, Narek N. Ishkhanyan, Olga N. Gulevskaya, Vladislav I. Chubinskiy-Nadezhdin, Evgenii D. Kryl’skii, Nadezhda A. Priymenko, Anna A. Klimovich, Elena V. Leychenko and Sergey A. Kozlov

Biomedicines 2026, 14(1), 60; https://doi.org/10.3390/biomedicines14010060 - 26 Dec 2025

Abstract

Background: Recently, data have been published about the inhibitory effect at low nanomolar concentrations on the TRPV1 ion channel for a new indole derivative named SV-1010. This molecule has also been shown to have a strong analgesic effect in mice and rats. [...] Read more.

Background: Recently, data have been published about the inhibitory effect at low nanomolar concentrations on the TRPV1 ion channel for a new indole derivative named SV-1010. This molecule has also been shown to have a strong analgesic effect in mice and rats. Since the biological target of SV-1010 is the TRPV1 ion channel, which plays an active role in inflammation, we conducted a series of animal tests to evaluate its potential as an anti-inflammatory agent. Methods: Nine different inflammatory agents were used to assess acute inflammation, and diclofenac was chosen as a positive control. Additionally SV-1010 effects in chronic proliferative and immunogenic inflammation models were also measured. Results: SV-1010 demonstrated a significant effect in most inflammatory tests, often surpassing that of diclofenac, and showed comparable efficacy to several other recognized anti-inflammatory drugs under certain conditions. The level of pro-inflammatory cytokines, TNF-α, IL-1β, and IL-6, exceeded after LPS administration was normalized to the non-LPS control group level by a dose of 0.1 mg/kg of SV-1010, and the effect was comparable to that of diclofenac at a dose of 12.5 mg/kg. The estimation by qPCR of the content of two enzymes, COX-2 and iNOS, which were increased by 10.8- and 19.4-fold, respectively, after LPS induction showed different molecular targets being utilized, manifested in the normalization of COX-2 content only after diclofenac treatment, and iNOS content only after SV-1010 treatment. Conclusions: Due to the simplicity of synthesis and low effective dose for mammal treatment, this compound can be interesting for a practice. Full article

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

15 pages, 1053 KB

Open AccessPerspective

Oxidative Stress as a Central Mechanistic Bridge Between Alzheimer’s and Vascular Pathologies in Mixed Dementia: Emerging Evidence and Therapeutic Perspectives

by Francesca Beretti, Marta Malenchini, Martina Gatti and Tullia Maraldi

Biomedicines 2026, 14(1), 59; https://doi.org/10.3390/biomedicines14010059 - 26 Dec 2025

Abstract

Mixed dementia (MD), characterized by overlapping features of Alzheimer’s disease (AD) and vascular dementia (VaD), represents the most prevalent form of late-life cognitive decline. Increasing evidence identifies oxidative stress as a unifying molecular mechanism driving both neurodegenerative and vascular pathologies in MD. Reactive [...] Read more.

Mixed dementia (MD), characterized by overlapping features of Alzheimer’s disease (AD) and vascular dementia (VaD), represents the most prevalent form of late-life cognitive decline. Increasing evidence identifies oxidative stress as a unifying molecular mechanism driving both neurodegenerative and vascular pathologies in MD. Reactive oxygen species (ROS) contribute to amyloid-β aggregation, tau hyperphosphorylation, endothelial dysfunction, and blood–brain barrier disruption, creating a self-perpetuating cycle of neuronal and vascular injury. Mechanistic models demonstrate how chronic hypoperfusion and mitochondrial dysfunction exacerbate ROS generation and neuroinflammation, while impaired Nrf2-mediated antioxidant defense further amplifies damage. Therapeutically, classical antioxidants show inconsistent efficacy, shifting focus toward mitochondrial protection, Nrf2 activation, and lifestyle-based oxidative load reduction. Therefore, we sought to outline therapeutic approaches capable of broadly targeting these mechanisms, through focused narrative analysis of recent studies employing delivery systems for antioxidant proteins and/or redox-regulating miRNAs. In particular, experimental interventions using mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) demonstrate neuroprotective and anti-inflammatory effects via the Nrf2 pathway, suggesting promising avenues for multimodal treatment. Integrating oxidative, vascular, and neurodegenerative paradigms is essential for advancing diagnostic precision and developing targeted interventions capable of addressing the complex pathophysiology of mixed dementia. Full article

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

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17 pages, 841 KB

Open AccessReview

Glial Activation, Neuroinflammation, and Loss of Neuroprotection in Chronic Pain: Cellular Mechanisms and Emerging Therapeutic Strategies

by Alyssa McKenzie, Rachel Dombrower, Nitchanan Theeraphapphong, Sophia McKenzie and Munther A. Hijazin

Biomedicines 2026, 14(1), 58; https://doi.org/10.3390/biomedicines14010058 - 26 Dec 2025

Abstract

Chronic pain is increasingly regarded as a condition of glia–neuronal dysregulation driven by persistent neuroinflammatory signaling. Following injury to nerves or tissues, glial cells, including astrocytes or satellite glial cells, undergo changes in their phenotype, thereby amplifying painful stimuli mediated by cytokines, chemokines, [...] Read more.

Chronic pain is increasingly regarded as a condition of glia–neuronal dysregulation driven by persistent neuroinflammatory signaling. Following injury to nerves or tissues, glial cells, including astrocytes or satellite glial cells, undergo changes in their phenotype, thereby amplifying painful stimuli mediated by cytokines, chemokines, or ATP signaling. In response to injuries, activated microglia release several mediators such as BDNF, IL-1β, or TNF-α, thereby disrupting chloride homeostasis and inducing disinhibition in the dorsal horn, and sustaining maladaptive neuroimmune activity. Dysfunction of astrocytes, characterized by impaired glutamate clearance via excitatory amino acid transporter 2 and elevated C-X-C motif chemokine ligand 1 (CXCL1) and ATP release, drives neuronal sensitization, loss of neuroprotective metabolic support, and persistence of pain. In peripheral ganglia, connexin–43–mediated satellite glial cell coupling leads to hyperexcitability, resulting in neuropathic and orofacial pain and contributing to peripheral neuroinflammation. Presently, there is no unified framework for glial cell types, and the molecular mechanisms underlying microglial, astrocyte, and satellite glial cell contributions to the transition to chronic pain from acute pain are not completely elucidated. This review synthesizes current evidence on cellular and molecular mechanisms linking glial reactivity to pain chronification through sustained neuroinflammatory remodeling and impaired neuroprotection. It evaluates therapeutic strategies, including purinergic receptor P2X4 and toll-like receptor 4 antagonists, to metabolic reprogramming, exosome therapy, and neuromodulation, aimed at restoring homeostatic glial function and re-establishing neuroprotective glia–neuron interactions. A deeper understanding of the temporal and spatial dynamics of glial activation may enable personalized, non-opioid interventions that not only achieve durable analgesia but also prevent progressive neuroinflammatory damage and support long-term functional recovery. Full article

(This article belongs to the Special Issue Neuroinflammation and Neuroprotection)

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31 pages, 4673 KB

Open AccessReview

The Extracellular Matrix and the Immune System in Acute Lung Injury: Partners in Damage and Repair

by Feiyan Xie, Yuheng Sun, Jing Wang, Wei Luo, Xinxin Zhang, Yusi Cheng and Jie Chao

Biomedicines 2026, 14(1), 57; https://doi.org/10.3390/biomedicines14010057 - 26 Dec 2025

Abstract

Acute lung injury (ALI) is driven by a complex interplay between immune dysregulation and structural matrix remodeling. Although inflammation, oxidative stress, and disturbances in the coagulation–fibrinolysis system have long been recognized as core pathogenic drivers, growing evidence demonstrates that the extracellular matrix (ECM) [...] Read more.

Acute lung injury (ALI) is driven by a complex interplay between immune dysregulation and structural matrix remodeling. Although inflammation, oxidative stress, and disturbances in the coagulation–fibrinolysis system have long been recognized as core pathogenic drivers, growing evidence demonstrates that the extracellular matrix (ECM) functions as an active regulator of lung injury and repair rather than a passive structural scaffold. This review synthesizes current advances in ECM biology and immunopathology to delineate how ECM remodeling influences, and is concurrently shaped by, the inflammatory microenvironment. We outline how biochemical and physical modes of ECM remodeling engage in bidirectional crosstalk with the immune system. Emerging therapeutic strategies targeting this ECM–immune axis are critically evaluated, including modulation of protease activity, interventions that reprogram cell–matrix interactions, and approaches that restore ECM integrity using stem cells or engineered biomaterials. By redefining ALI as a disease of immune–matrix reciprocity, this review underscores the ECM as both a structural framework and a dynamic immunoregulatory hub, providing conceptual and mechanistic insights that may guide the development of precision therapies for ALI and related pulmonary disorders. Full article

(This article belongs to the Section Immunology and Immunotherapy)

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14 pages, 889 KB

Open AccessArticle

Title Autogenous Tooth Bone Grafts with Enamel Matrix Derivates in Non-Contained Intrabony Periodontal Defects—A Case Series Study

by Eleonora Solyom, Kristóf Forgó, Kristof Somodi, Daniel Palkovics, Szilard Vancsa, Peter Windisch, Balint Molnar and Reka Fazekas

Biomedicines 2026, 14(1), 56; https://doi.org/10.3390/biomedicines14010056 - 26 Dec 2025

Abstract

Background: The predictability of regenerative outcomes in non-contained intrabony periodontal defects remains limited. Autogenous tooth bone grafts (ATB) may represent a biologically active and osteoconductive scaffold with minimal residual graft material. This study evaluated the clinical and radiographic outcomes of ATB combined with [...] Read more.

Background: The predictability of regenerative outcomes in non-contained intrabony periodontal defects remains limited. Autogenous tooth bone grafts (ATB) may represent a biologically active and osteoconductive scaffold with minimal residual graft material. This study evaluated the clinical and radiographic outcomes of ATB combined with enamel matrix derivative (EMD) in intrabony defects. Methods: Nine systemically healthy patients (15 defects) were treated with ATB + EMD in a retrospective proof-of-concept design. Clinical parameters—probing pocket depth (PPD), clinical attachment level (CAL), and gingival recession (GR)—were recorded at baseline and 6 months. Radiographic changes in defect depth and width were also assessed. Statistical significance was set at p < 0.05. Results: Mean PPD decreased from 7.73 ± 0.96 mm to 3.87 ± 0.74 mm (p < 0.001), and CAL improved from 9.20 ± 1.47 mm to 5.53 ± 1.36 mm (p < 0.001). GR changes were not significant. Radiographically, mean defect depth and width were reduced from 3.81 ± 1.59 mm and 2.56 ± 0.75 mm to 0.72 ± 1.08 mm and 0.44 ± 0.70 mm, respectively (p < 0.001). Conclusions: The combination of ATB and EMD yielded substantial clinical and radiographic improvements in intrabony periodontal defects. These findings suggest that autogenous tooth bone grafts may serve as a reliable biologically active scaffold for regenerative periodontal surgery. This is the first study evaluating the combination of EMD and ATB. Within the study limitations, ATB + EMD demonstrated promising regenerative potential, warranting future controlled clinical trials. Full article

(This article belongs to the Special Issue Periodontal Disease and Periodontal Tissue Regeneration—Second Edition)

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21 pages, 610 KB

Open AccessReview

Advances in Understanding the Impact of Human Gut Microbiota on Chemotherapy-Induced Neutropenia

by Mengyuan He, Liangkang Lin, Cheng Ouyang, Su Liu and Chun Chen

Biomedicines 2026, 14(1), 55; https://doi.org/10.3390/biomedicines14010055 - 26 Dec 2025

Abstract

Neutrophils play a crucial role in defending against bacterial and fungal pathogens; however, chemotherapy reduces neutrophil counts, increasing infection risk and worsening cancer treatment outcomes. Emerging evidence highlights the gut microbiota as a promising biomarker and therapeutic target for chemotherapy-induced neutropenia (CIN). Here, [...] Read more.

Neutrophils play a crucial role in defending against bacterial and fungal pathogens; however, chemotherapy reduces neutrophil counts, increasing infection risk and worsening cancer treatment outcomes. Emerging evidence highlights the gut microbiota as a promising biomarker and therapeutic target for chemotherapy-induced neutropenia (CIN). Here, we review current knowledge regarding the relationship between the gut microbiota and CIN, summarizing the mechanisms by which the microbiota influence neutrophil dynamics, current therapeutic approaches, and limitations in regard to preserving microbiota stability. This review offers a theoretical foundation for “gut-protective” chemotherapy, potentially facilitating personalized treatments, although clinical translation remains challenging. Full article

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

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