Biomedicines

10 pages, 1413 KiB

Open AccessCase Report

Managing Urethral Diverticulum During Pregnancy Utilizing Advanced Ultrasonographic Techniques: A Literature Review and Case Study

by Desirèe De Vicari, Marta Barba, Alice Cola and Matteo Frigerio

Biomedicines 2025, 13(6), 1432; https://doi.org/10.3390/biomedicines13061432 (registering DOI) - 11 Jun 2025

Abstract

Urethral diverticulum (UD) during pregnancy is a rare clinical condition, with limited literature available to guide standardized management. Fewer than a dozen well-documented cases have been reported, but they reflect a wide range of clinical approaches from antenatal surgery to postpartum intervention. We [...] Read more.

Urethral diverticulum (UD) during pregnancy is a rare clinical condition, with limited literature available to guide standardized management. Fewer than a dozen well-documented cases have been reported, but they reflect a wide range of clinical approaches from antenatal surgery to postpartum intervention. We report the case of a 36-year-old woman diagnosed at 34 weeks of gestation with a 5.5 cm urethral diverticulum, presenting with suprapubic pain, urinary dribbling, and green vaginal discharge. Conservative management was pursued due to obstetric concerns, including multiple uterine fibroids and risk of preterm labor. Advanced ultrasonographic techniques—biplane transvaginal imaging, transperineal ultrasound, and 3D surface rendering—enabled a detailed anatomical assessment of parameters including the lesion’s size, shape, and relationship to the urethra, without resorting to invasive diagnostics. The diverticulum was found to cause 90° urethral angulation and had a C-shaped configuration, with a volume of 11.5 cm³. Following antibiotic treatment, the patient’s symptoms improved, and she remained clinically stable. She was scheduled for vaginal delivery followed by postpartum diverticulectomy. This case illustrates the diagnostic value of high-resolution ultrasound in pregnancy and supports literature recommendations favoring conservative treatment and delayed surgery to reduce maternal and fetal risk. Vaginal delivery remains a viable option in select UD cases. Full article

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

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14 pages, 4795 KiB

Open AccessArticle

Analysis of Energy Metabolism and Lipid Spatial Distribution in Hypoxic-Ischemic Encephalopathy Revealed by MALDI-MSI

by Xingxing Zhao, Peipei Chen, Lun Yu, Chuchu Gao, Sannan Wang, Zuming Yang and Zongtai Feng

Biomedicines 2025, 13(6), 1431; https://doi.org/10.3390/biomedicines13061431 (registering DOI) - 11 Jun 2025

Abstract

Background: Neonatal hypoxic-ischemic encephalopathy (HIE) is a major cause of neonatal death and neurodevelopmental disorders, and its pathological mechanisms are closely related to disturbed energy metabolism and lipid remodeling. Exploring the spatial heterogeneity of metabolomics is essential to analyze the pathological process of [...] Read more.

Background: Neonatal hypoxic-ischemic encephalopathy (HIE) is a major cause of neonatal death and neurodevelopmental disorders, and its pathological mechanisms are closely related to disturbed energy metabolism and lipid remodeling. Exploring the spatial heterogeneity of metabolomics is essential to analyze the pathological process of HIE. Methods: In this study, we established a neonatal mouse hypoxic-ischemic brain damage (HIBD) model by the modified Rice method, and analyzed various metabolic pathways such as the tricarboxylic acid (TCA) cycle, purine metabolism, and lipid metabolism in the ischemic edema area, with contralateral and control brain tissues using matrix-assisted laser desorption mass spectrometry imaging (MALDI-MSI) with a spatial resolution of 50 μm. Results: In the HIBD model, key metabolites of the tricarboxylic acid (TCA) cycle (citrate, succinate, L-glutamate, glucose, aspartate, and glutamine) were significantly enriched in the edematous area compared with the control (fold change: 1.52–2.82), which suggests a blockage of mitochondrial function; ATP/ADP/AMP levels were reduced by 53–73% in the edematous area, and xanthine was abnormally accumulated in the hippocampus of the affected side, suggesting energy depletion and altered purine metabolism; lipid remodeling showed regional specificity: some unsaturated fatty acids, such as docosahexaenoic acid, were abnormally accumulated in the hippocampus. In contrast, pentadecanoic acid levels were reduced across the entire brain in the HIBD model, with a more pronounced decrease in the ipsilateral hippocampus, suggesting impaired membrane stability. Conclusions: The neonatal mouse HIBD model exhibits reprogramming of energy metabolism, characterized by a blockage in the tricarboxylic acid (TCA) cycle and ATP depletion, along with an abnormal spatial distribution of lipids. By targeting xanthine metabolic pathways, restoring mitochondrial function, and intervening in region-specific lipid remodeling, brain energy homeostasis may be improved and neurological damage attenuated. Further studies should validate the clinical feasibility of xanthine and lipid imbalance as diagnostic markers of HIBD and explore the critical time window for metabolic intervention to optimize therapeutic strategies. Full article

(This article belongs to the Special Issue Genetic Research on Neuropsychiatric Disorders and Complex Human Diseases)

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19 pages, 2715 KiB

Open AccessArticle

Kiperin Postbiotic Supplement-Enhanced Bacterial Supernatants Promote Fibroblast Function: Implications for Regenerative Medicine

by Lutfiye Karcioglu Batur, Cuneyd Yavas, Yağmur Ekenoğlu Merdan and Ashabil Aygan

Biomedicines 2025, 13(6), 1430; https://doi.org/10.3390/biomedicines13061430 - 10 Jun 2025

Abstract

Background/Objectives: Kiperin Postbiotics, defined as non-viable metabolic products derived from probiotics, have gained attention as potential modulators of cellular responses involved in tissue repair. This study aimed to evaluate the effects of a postbiotic supplement (PS)—composed of inactivated strains of Escherichia coli, [...] Read more.

Background/Objectives: Kiperin Postbiotics, defined as non-viable metabolic products derived from probiotics, have gained attention as potential modulators of cellular responses involved in tissue repair. This study aimed to evaluate the effects of a postbiotic supplement (PS)—composed of inactivated strains of Escherichia coli, Lacticaseibacillus rhamnosus, and Lactiplantibacillus plantarum—on fibroblast function, particularly in the context of bacterial secretomes from common pathogenic strains. Methods: Human fibroblast cell lines (HFF-1 and CCD-18Co) were treated with cell-free supernatants (CFS) from E. coli ATCC 25922, Staphylococcus aureus ATCC 29213, and Enterococcus faecalis ATCC 29212, either alone or in combination with the PS. Assessments included cell count, migration (via scratch assay), oxidative stress levels, and expression of immune-related genes (IL-6, IL-10, TNF-α, DRD4). Results: CFS from E. faecalis significantly increased fibroblast counts, whereas E. coli and S. aureus CFS reduced cell counts and elevated oxidative stress. Co-treatment with PS reversed these effects in a strain-dependent manner by lowering oxidative stress and partially restoring cell proliferation. Scratch assays demonstrated enhanced migration in PS-treated fibroblasts. Gene expression analyses revealed no statistically significant changes, though variable trends were observed across treatment groups. Conclusions: PS may mitigate the harmful effects of certain bacterial secretomes while preserving or enhancing beneficial ones. Its ability to reduce oxidative stress and promote fibroblast proliferation and migration suggests a potential pro-regenerative role in vitro. Although gene expression changes were limited, the results offer initial insights into the underlying molecular responses influenced by postbiotic supplementation. Full article

(This article belongs to the Section Microbiology in Human Health and Disease)

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23 pages, 2556 KiB

Open AccessReview

Immunometabolic Interactions in Obesity: Implications for Therapeutic Strategies

by Qin Fei, Jueru Huang, Yi He, Yufeng Zhang, Xiaojun Zhang, Jing Wang and Qiang Fu

Biomedicines 2025, 13(6), 1429; https://doi.org/10.3390/biomedicines13061429 - 10 Jun 2025

Abstract

Obesity is characterized by excessive fat accumulation that triggers chronic low-grade inflammation and systemic immune dysregulation, significantly increasing the risk of metabolic disorders including insulin resistance, type 2 diabetes, and cardiovascular disease. This review examines the bidirectional relationship between obesity and immune dysfunction, [...] Read more.

Obesity is characterized by excessive fat accumulation that triggers chronic low-grade inflammation and systemic immune dysregulation, significantly increasing the risk of metabolic disorders including insulin resistance, type 2 diabetes, and cardiovascular disease. This review examines the bidirectional relationship between obesity and immune dysfunction, focusing on how immune cell infiltration in adipose tissue drives inflammatory processes. We highlight the phenotypic shifts in key immune populations—macrophages polarized toward proinflammatory M1 phenotypes, T cell exhaustion occurrs, and alterations appear in B cells, natural killer (NK) cells, and dendritic cells—that collectively contribute to metabolic deterioration. The gut microbiome emerged as a critical mediator in this relationship, influencing both immune responses and metabolic regulation through gut–liver and gut–brain axes. We explore emerging immunomodulatory therapeutic strategies, including anti-inflammatory agents, microbiota interventions, and targeted immune therapies such as innovative nanomedicine approaches. The review also addresses the challenges of immunotherapy in obesity, particularly the paradoxical effects observed in cancer immunotherapy outcomes and the need for personalized treatment approaches. Artificial intelligence is highlighted as a potential tool to enhance patient stratification and treatment optimization in future immunomodulatory interventions. Understanding these immunometabolic interactions provides a foundation for developing more effective therapeutic strategies that could transform obesity management and reduce the burden of obesity-related metabolic diseases. Full article

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

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7 pages, 267 KiB

Open AccessArticle

New Clinical View on the Relationship Between the Diameter of the Deep Femoral Artery and Sex: Index δ-Anatomical and Radiological Study

by Piotr Łabętowicz, Nicol Zielinska, Dawid Pilewski, Łukasz Olewnik and Kacper Ruzik

Biomedicines 2025, 13(6), 1428; https://doi.org/10.3390/biomedicines13061428 - 10 Jun 2025

Abstract

Background: The femoral artery is a continuation of the external iliac artery. Knowledge of the topography and morphological variability of the thigh vessels informs various fields of medicine, such as hip replacement, hip fracture and femoral trochanter fracture, embolectomy, and angiography. The main [...] Read more.

Background: The femoral artery is a continuation of the external iliac artery. Knowledge of the topography and morphological variability of the thigh vessels informs various fields of medicine, such as hip replacement, hip fracture and femoral trochanter fracture, embolectomy, and angiography. The main aim of this study was to calculate the δ index from morphological measurements. We introduce the δ index to quantify the relative dominance of the DFA in supplying the thigh, aiming to improve clinical assessment and procedural planning. Methods: The study comprised two parts: anatomical dissection and radiological examination. During the anatomical study, 80 lower limbs (34 female and 46 male) fixed in 10% formalin were dissected. For the radiological study, angio-CT scans of the lower limbs of 100 patients (200 lower limbs) were analyzed. In both studies, the δ index was determined. This is the ratio of the diameter of the deep femoral artery at its point of origin to the diameter of the femoral artery after that origin. The morphometric measurements were analyzed statistically using Statistica 12.0 software. Results: The average values of the δ index for the right side were 0.95 (±0.23) and 0.89 (±0.21), respectively, in the anatomical and radiological studies, while for the left side they were 0.94 (±0.23) and 0.89 (±0.27), respectively. The average values for males were 0.88 (±0.18) and 0.80 (±0.17), respectively, while for females they were 1.04 (±0.26) and 1.12 (±0.23), respectively. Conclusions: The δ index, elaborated and calculated in anatomical and radiological studies, showed no statistically significant body side difference. However, it showed a statistically significant sex difference; there was a greater distribution of blood through the deep femoral artery in women than in men. Full article

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

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60 pages, 2510 KiB

Open AccessReview

Animal Models of Spinal Cord Injury

by Vladislav E Sobolev, Yuriy I. Sysoev, Tatiana V. Vyunova and Pavel E. Musienko

Biomedicines 2025, 13(6), 1427; https://doi.org/10.3390/biomedicines13061427 - 10 Jun 2025

Abstract

Spinal cord injury (SCI) is one of the most frequent causes of disability, accompanied by motor and postural impairments, as well as autonomic and behavioural disorders. Since the beginning of the last century, researchers have been developing and refining experimental models of SCI [...] Read more.

Spinal cord injury (SCI) is one of the most frequent causes of disability, accompanied by motor and postural impairments, as well as autonomic and behavioural disorders. Since the beginning of the last century, researchers have been developing and refining experimental models of SCI to study pathogenesis and find therapies. Since the beginning of the 20th century, quite a wide range of methods have been developed for contusion and compression injury, complete and partial transection of the spinal cord, and many others. The choice of model subject in such studies was not limited to mammals, but also included amphibians, lampreys, and even fish. Many functional tests have been proposed to assess functional recovery after injury in laboratory animals, ranging from simple rating scales to locomotion kinematics or recording of spinal neuronal activity. This review describes existing models of SCI in most animal species used in neurobiology. Their key characteristics are discussed, which determine the choice of model and model animals depending on the experimental tasks. Each experimental model of SCI has its own advantages and disadvantages determined by species-specific features of spinal cord anatomy and physiology, the speed of recovery from injury, and the ratio of the necrosis zone to the penumbra. The applicability and availability of the proposed methods for assessing the speed and completeness of recovery is also an important factor. Full article

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

26 pages, 21466 KiB

Open AccessReview

Point-of-Care Ultrasound Use in Hemodynamic Assessment

by Ahmed Noor, Margaret Liu, Alan Jarman, Travis Yamanaka and Malvika Kaul

Biomedicines 2025, 13(6), 1426; https://doi.org/10.3390/biomedicines13061426 - 10 Jun 2025

Abstract

Hemodynamic assessment is critical in emergency and critical care for preventing, diagnosing, and managing shock states that significantly affect patient outcomes. Point-of-care ultrasound (POCUS) has become an invaluable, non-invasive, real-time, and reproducible tool for bedside decision-making. Advancements such as Doppler imaging, advanced critical [...] Read more.

Hemodynamic assessment is critical in emergency and critical care for preventing, diagnosing, and managing shock states that significantly affect patient outcomes. Point-of-care ultrasound (POCUS) has become an invaluable, non-invasive, real-time, and reproducible tool for bedside decision-making. Advancements such as Doppler imaging, advanced critical care ultrasonography, and transesophageal echocardiography (TEE) have expanded its utility, enabling rapid and repeatable evaluations, especially in complex mixed shock presentations. This review explores the role of POCUS in hemodynamic monitoring, emphasizing its ability to assess cardiac output, filling pressures, and vascular congestion, facilitating shock classification and guiding fluid management. We highlight an extensive array of POCUS techniques for evaluating right and left cardiac function and review existing literature on their advantages, limitations, and appropriate clinical applications. Beyond assessing volume status, this review discusses the role of POCUS in predicting fluid responsiveness and supporting more individualized, precise management strategies. Ultimately, while POCUS is a powerful tool for rapid, comprehensive hemodynamic assessment in acute settings, its limitations must be acknowledged and thoughtfully integrated into clinical decision-making. Full article

(This article belongs to the Special Issue Advanced Research in Cardiovascular and Hemodynamic Monitoring)

21 pages, 686 KiB

Open AccessReview

Unraveling the Roles of Macrophages in Vascularized Composite Allotransplantation

by Hui-Yun Cheng, Madonna Rica Anggelia and Cheng-Hung Lin

Biomedicines 2025, 13(6), 1425; https://doi.org/10.3390/biomedicines13061425 - 10 Jun 2025

Abstract

The phenotypic heterogeneity and functional diversity of macrophages have been increasingly appreciated, particularly regarding their roles as innate immune cells in shaping transplantation outcomes. However, their functions in vascularized composite allotransplantation (VCA) remain underexplored. In this review, we first describe the development of [...] Read more.

The phenotypic heterogeneity and functional diversity of macrophages have been increasingly appreciated, particularly regarding their roles as innate immune cells in shaping transplantation outcomes. However, their functions in vascularized composite allotransplantation (VCA) remain underexplored. In this review, we first describe the development of macrophages and the heterogeneity of macrophage differentiation, then present current insights into macrophages’ involvement across key stages of VCA, including ischemia–reperfusion injury at the peri-transplantation stage, and the outcomes following transplantation, including acute rejection, chronic rejection, and development of transplantation tolerance. The existing evidence supports that macrophages significantly influence both short- and long-term VCA graft survival. The presence of vascularized bone marrow within some VCA grafts further suggests the involvement of donor bone marrow-derived macrophage population and adds another layer of complexity to immune dynamics. Collectively, current understanding highlights the macrophage as a promising target for therapeutic intervention and warrants continued investigation into their diverse functions and potential for improving VCA outcomes. Full article

(This article belongs to the Special Issue An Update on Transplantation Immunology)

30 pages, 1318 KiB

Open AccessReview

Pathogenesis and Therapeutic Perspectives of Tubular Injury in Diabetic Kidney Disease: An Update

by Jiamian Geng, Sijia Ma, Hui Tang and Chun Zhang

Biomedicines 2025, 13(6), 1424; https://doi.org/10.3390/biomedicines13061424 - 10 Jun 2025

Abstract

Diabetic kidney disease (DKD), a well-characterized microvascular complication associated with the progression of diabetes mellitus, has been identified as the leading etiological factor contributing to the global burden of end-stage kidney disease (ESKD). Historically, DKD research has predominantly centered on glomerular mechanisms; however, [...] Read more.

Diabetic kidney disease (DKD), a well-characterized microvascular complication associated with the progression of diabetes mellitus, has been identified as the leading etiological factor contributing to the global burden of end-stage kidney disease (ESKD). Historically, DKD research has predominantly centered on glomerular mechanisms; however, recent studies have increasingly emphasized the critical role of tubular dysfunction. Extensive evidence has elucidated the key pathological drivers of tubular injury in DKD, encompassing metabolic dysregulation, pro-inflammatory signaling pathways, diverse cellular stress responses, and epithelial–mesenchymal transition (EMT). Furthermore, emerging mechanistic studies reveal that autophagic flux impairment and epigenetic memory formation collaboratively drive cellular senescence in DKD. Regarding the treatment of DKD, various hypoglycemic drugs, as well as hypotensive drugs, and microcirculatory improvers have garnered significant attention. Recently, stem cell-based interventions and precision gene editing techniques have unveiled novel therapeutic paradigms for DKD, fundamentally expanding the treatment arsenal beyond conventional pharmacotherapy. This review synthesizes updated insights into the pathogenesis of tubular injury in DKD and highlights promising therapeutic strategies for managing this condition. Full article

(This article belongs to the Special Issue Diabetes: Comorbidities, Therapeutics and Insights (2nd Edition))

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23 pages, 389 KiB

Open AccessReview

New and Emerging Biomarkers in Chronic Kidney Disease

by Mikołaj Dopierała, Nadja Nitz, Oliwia Król, Karolina Wasicka-Przewoźna, Krzysztof Schwermer and Krzysztof Pawlaczyk

Biomedicines 2025, 13(6), 1423; https://doi.org/10.3390/biomedicines13061423 - 10 Jun 2025

Abstract

Chronic kidney disease (CKD) represents a major and widespread global health challenge. It affects over 800 million people worldwide, which is approximately 13% of the world’s population. Over the past 20 years, it has consistently ranked among the leading causes of death. As [...] Read more.

Chronic kidney disease (CKD) represents a major and widespread global health challenge. It affects over 800 million people worldwide, which is approximately 13% of the world’s population. Over the past 20 years, it has consistently ranked among the leading causes of death. As a result of its typically painless and asymptomatic presentation in the early stages of the disease, CKD is frequently diagnosed late, when the patient is already suffering from serious complications. In recent years, studies have identified novel biomarkers associated with the pathophysiology of CKD, including chronic inflammation, tubular injury, and CKD-related outcomes such as bone and mineral metabolism disorders, cardiovascular events, and all-cause mortality. Identifying and using these emerging biomarkers—like kidney injury molecule, N-acetyl–D-glucosaminidase, ficolins, the NLRP3 (nucleotide-binding domain, leucine-rich–containing family, pyrin domain–containing-3) inflammasome, soluble suppression of tumorigenicity-2, galectin-3, growth differentiation factor-15, soluble urokinase-type plasminogen activator receptor, sclerostin, the Dick-kopf proteins, and indexes such as the systemic inflammation response index—may lead to a significant advancement in early diagnosis, risk stratification, and personalized treatment strategies for CKD patients. Despite their potential, the routine clinical use of these novel biomarkers remains limited due to challenges such as high costs and the lack of standardized testing methods. There is still considerable room for advancement in both the diagnosis and management of CKD. Hopefully, increasingly more new biomarkers will become usable in clinical practice, ultimately improving care quality and outcomes for patients with CKD. Full article

(This article belongs to the Special Issue New Advances in Chronic Kidney Disease: Biology, Diagnosis and Therapy (2nd Edition))

36 pages, 1531 KiB

Open AccessReview

Orchestration of Gut–Liver-Associated Transcription Factors in MAFLD: From Cross-Organ Interactions to Therapeutic Innovation

by Ao Liu, Mengting Huang, Yuwen Xi, Xiaoling Deng and Keshu Xu

Biomedicines 2025, 13(6), 1422; https://doi.org/10.3390/biomedicines13061422 - 10 Jun 2025

Abstract

Metabolic dysfunction-associated fatty liver disease (MAFLD) represents a global health burden, however, therapeutic advancements remain hindered by incomplete insights on mechanisms and suboptimal clinical interventions. This review focused on the transcription factors (TFs) associated with the gut–liver axis, emphasizing their roles as molecular [...] Read more.

Metabolic dysfunction-associated fatty liver disease (MAFLD) represents a global health burden, however, therapeutic advancements remain hindered by incomplete insights on mechanisms and suboptimal clinical interventions. This review focused on the transcription factors (TFs) associated with the gut–liver axis, emphasizing their roles as molecular interpreters of systemic crosstalk in MAFLD. We delineate how TF networks integrate metabolic, immune, and gut microbial signals to manage hepatic steatosis, inflammation, and fibrosis. For instance, metabolic TFs such as peroxisome proliferator-activated receptor α (PPARα) and farnesoid X receptor (FXR) are responsible for regulating lipid oxidation and bile acid homeostasis, while immune-related TFs like signal transducer and activator of transcription 3 (STAT3) modulate inflammatory cascades involving immune cells. Emerging evidence highlights microbiota-responsive TFs, like hypoxia-inducible factor 2α (HIF2α) and aryl hydrocarbon receptor (AHR), linking microbial metabolite signaling to hepatic metabolic reprogramming. Critically, TF-centric therapeutic strategies, including selective TF-agonists, small molecules targeted to degrade TF, and microbiota modulation, hold considerable promise for treating MAFLD. By synthesizing these insights, this review underscores the necessity to dissect TF-mediated interorgan communication and proposes a roadmap for translating mechanism discoveries into precision therapies. Future research should prioritize the use of multi-omics approaches to map TF interactions and validate their clinical relevance to MAFLD. Full article

(This article belongs to the Special Issue New Insights Into Non-Alcoholic Fatty Liver Diseases)

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4 pages, 169 KiB

Open AccessEditorial

Advancing Precision in IBD Care: Innovations in Diagnosis, Monitoring, and Multidisciplinary Management

by Pedro Vilela Teixeira, Fernando Magro and Maria Manuela Estevinho

Biomedicines 2025, 13(6), 1421; https://doi.org/10.3390/biomedicines13061421 - 10 Jun 2025

Abstract

Inflammatory bowel disease (IBD), encompassing Crohn’s disease (CD) and ulcerative colitis (UC), is a multifactorial disorder involving a dynamic interplay between genetic susceptibility, gut microbiota, nutrition, environmental exposures, immune dysregulation, and psychosocial factors [...] Full article

(This article belongs to the Special Issue Inflammatory Bowel Diseases: New Diagnostic and Therapeutic Approaches)

30 pages, 1795 KiB

Open AccessReview

Computational Neuroscience’s Influence on Autism Neuro-Transmission Research: Mapping Serotonin, Dopamine, Gaba, and Glutamate

by Victoria Bamicha, Pantelis Pergantis, Charalabos Skianis and Athanasios Drigas

Biomedicines 2025, 13(6), 1420; https://doi.org/10.3390/biomedicines13061420 - 10 Jun 2025

Abstract

Autism spectrum disorder is a complex and diverse neurobiological condition. Understanding the mechanisms and causes of the disorder requires an in-depth study and modeling of the immune, mitochondrial, and neurological systems. Computational neuroscience enhances psychiatric science by employing machine learning techniques on neural [...] Read more.

Autism spectrum disorder is a complex and diverse neurobiological condition. Understanding the mechanisms and causes of the disorder requires an in-depth study and modeling of the immune, mitochondrial, and neurological systems. Computational neuroscience enhances psychiatric science by employing machine learning techniques on neural networks, combining data on brain activity with the pathophysiological and biological characteristics of psychiatric–neurobiological disorders. The research explores the integration of neurotransmitter activity into computational models and their potential roles in diagnosing and treating autism using computational methods. This research employs a narrative review that focuses on four neurotransmitter systems directly related to the manifestation of autism, specifically the following neurotransmitters: serotonin, dopamine, glutamate, and gamma-aminobutyric acid (GABA). This study reveals that computational neuroscience advances autism diagnosis and treatment by identifying genetic factors and improving the efficiency of diagnosis. Neurotransmitters play a crucial role in the function of brain cells, enhancing synaptic conduction and signal transmission. However, the interaction of chemical compounds with genetic factors and network alterations influences the pathophysiology of autism. This study integrates the investigation of computational approaches in four neurotransmitter systems associated with ASD. It improves our understanding of the disorder and provides insights that could stimulate further research, thereby contributing to the development of effective treatments. Full article

(This article belongs to the Special Issue Dualistic Equilibrium in Neurotransmission and Beyond: Unraveling the Pathophysiology and Unlocking Novel Therapeutic Targets in Neuropsychiatric Disorders—2nd Edition)

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17 pages, 5508 KiB

Open AccessReview

Application of Synchrotron Radiation in Fundamental Research and Clinical Medicine

by Chao Xiao, Jinde Zhang, Yang Li, Mingyuan Xie and Dongbai Sun

Biomedicines 2025, 13(6), 1419; https://doi.org/10.3390/biomedicines13061419 - 10 Jun 2025

Abstract

Synchrotron radiation light sources have been successfully utilized in material science, biomedicine, and other fields due to their high intensity, excellent monochromaticity, coherence, and collimation. In recent years, synchrotron radiation has significantly expedited the advancement of medical applications, particularly through innovations in imaging [...] Read more.

Synchrotron radiation light sources have been successfully utilized in material science, biomedicine, and other fields due to their high intensity, excellent monochromaticity, coherence, and collimation. In recent years, synchrotron radiation has significantly expedited the advancement of medical applications, particularly through innovations in imaging and radiotherapy. For instance, synchrotron X-ray imaging has enabled high-contrast and spatial–temporal resolution images for early-stage diagnosis of breast cancer and cardiovascular diseases, offering superior diagnostic accuracy compared to conventional methods. Additionally, novel synchrotron radiation-based radiotherapy techniques, such as microbeam therapy and stereotactic radiotherapy, have shown great potential for clinical application by enabling precise tumor targeting while minimizing damage to surrounding healthy tissues. These advancements are projected to redefine imaging diagnostics and therapeutic strategies, particularly for resistant cancers, by offering enhanced precision, reduced radiation doses, and improved therapeutic outcomes. This review provides an overview of synchrotron radiation beamline characteristics, recent breakthroughs in imaging and radiotherapy, and their emerging applications in treating heart, breast, lung, bone, and brain conditions. Full article

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

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16 pages, 1060 KiB

Open AccessReview

Glucocorticoid Insensitivity: Is It a Question of Time and Place?

by Christopher Lambers and Michael Roth

Biomedicines 2025, 13(6), 1418; https://doi.org/10.3390/biomedicines13061418 - 10 Jun 2025

Abstract

Background: Glucocorticoid insensitivity is a problem for the therapy of chronic inflammatory lung diseases, such as asthma and chronic obstructive pulmonary disease (COPD). Both are non-communicable chronic inflammatory lung diseases with worldwide increasing incidences. Only symptoms can be controlled by inhaled or systemic [...] Read more.

Background: Glucocorticoid insensitivity is a problem for the therapy of chronic inflammatory lung diseases, such as asthma and chronic obstructive pulmonary disease (COPD). Both are non-communicable chronic inflammatory lung diseases with worldwide increasing incidences. Only symptoms can be controlled by inhaled or systemic glucocorticoids, often combined with β2 agonists and/or muscarinic receptor antagonists. The therapeutic effect of glucocorticoids varies between individuals, and a significant number of patients do not respond well. It is believed that only protein-free circulating unbound glucocorticoids can enter cells by diffusion and achieve their therapeutic effect by binding to the intracellular glucocorticoid receptor (GR), encoded by the NR3C1 gene, for which over 3000 single-nucleotide polymorphisms have been described. In addition, various GR protein isoforms result from 11 transcription start sites, and differential mRNA splicing leads to further GR protein variants; each can be modified post-translational and alter steroid response. To add more variety, some GR isoforms are expressed cell-type specific or in a sub-cellular location. The GR only functions when it forms a complex with other intracellular proteins that regulate ligand binding, cytosol-to-nuclear transport, and nuclear and cytosolic action. Importantly, the timing of the GR activity can be cell type, time, and condition specific. These factors are rarely considered when assessing disease-specific loss or reduced GR response. Conclusions: Future studies should analyze the timing of the availability, activity, and interaction of all components of the glucocorticoid signaling cascade(s) and compare these factors between non-diseased and diseased probands, applying the combination of all omics methods (250). Full article

(This article belongs to the Special Issue Unraveling the Role of Glucocorticoid Receptor in Inflammation and Cancer)

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5 pages, 166 KiB

Open AccessEditorial

PLpro Inhibitors as a Potential Treatment for COVID-19

by Yu Han and Feng Xu

Biomedicines 2025, 13(6), 1417; https://doi.org/10.3390/biomedicines13061417 - 10 Jun 2025

Abstract

The advent of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the subsequent coronavirus disease 2019 (COVID-19) pandemic have posed a serious threat to human health and society [...] Full article

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

18 pages, 7530 KiB

Open AccessArticle

Mechanisms Underlying Hyperexcitability: Combining Mossy Fiber Sprouting and Mossy Cell Loss in Neural Network Model of the Dentate Gyrus

by Dariusz Świetlik

Biomedicines 2025, 13(6), 1416; https://doi.org/10.3390/biomedicines13061416 - 9 Jun 2025

Abstract

Background/Objectives: A concussive head injury increases the likelihood of temporal lobe epilepsy through mechanisms that are not entirely understood. This study aimed to investigate how two key histopathological features shared by both TLE (temporal lobe epilepsy) and head injury—mossy fiber sprouting and [...] Read more.

Background/Objectives: A concussive head injury increases the likelihood of temporal lobe epilepsy through mechanisms that are not entirely understood. This study aimed to investigate how two key histopathological features shared by both TLE (temporal lobe epilepsy) and head injury—mossy fiber sprouting and hilar excitatory cell loss—contribute to the modulation of dentate gyrus excitability. Methods: A computational approach was used to explore the impact of specific levels of mossy fiber sprouting and mossy cell loss, while avoiding the confounding effects of concurrent changes. The dentate gyrus model consists of 500 granule cells, 15 mossy cells, 6 basket cells and 6 hilar perforant path-associated cells. Results: My simulations demonstrate a correlation between the degree of mossy fiber sprouting and the number of spikes in dentate gyrus granule cells (correlations coefficient R = 0.95, p < 0.0001) and other cells (correlations coefficient R = 0.99, p < 0.0001). The mean values (standard deviation, SD) and 95% CI for granule cell activity in the control group and percentage 10–50% of mossy fiber sprouting groups are 376.4 (16.7) (95% CI, 374.9–377.8) vs. 463.5 (24.3) (95% CI, 461.4–465.6) vs. 514.8 (32.5) (95% CI, 511.9–517.6) vs. 555.0 (40.4) (95% CI, 551.5–558.6) vs. 633.4 (51.8) (95% CI, 628.8–637.9) vs. 701.7 (66.2) (95% CI, 695.9–707.5). The increase in mossy fiber sprouting was significantly statistically associated with an increase in granule cell activity (p < 0.01). The removal of mossy cells led to a reduction in excitability within the model network (for granule cells, correlations coefficient R = −0.40, p < 0.0001). Conclusions: These results are generally consistent with experimental observations, which indicate a high degree of mossy fiber sprouting in animals with a higher frequency of seizures. Whereas unlike the strong hyperexcitability effects induced by mossy fiber sprouting, the removal of mossy cells led to reduced granule cell responses to perforant path activation. Full article

(This article belongs to the Special Issue Brain Injury: New Insights into Mechanisms and Future Promising Treatments—Second Edition)

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34 pages, 2005 KiB

Open AccessReview

Peptide-Based Nanoparticle for Tumor Therapy

by Phonpilas Thongpon, Menghuan Tang and Zhaoqing Cong

Biomedicines 2025, 13(6), 1415; https://doi.org/10.3390/biomedicines13061415 (registering DOI) - 9 Jun 2025

Abstract

Cancer treatment continues to face significant challenges due to the limitations of conventional therapies, including non-specific toxicity, poor bioavailability, and drug resistance. Nanotechnology, particularly peptide-based nanoparticles (NPs), is increasingly recognized as a valuable strategy to address these obstacles. Peptides provide a versatile platform [...] Read more.

Cancer treatment continues to face significant challenges due to the limitations of conventional therapies, including non-specific toxicity, poor bioavailability, and drug resistance. Nanotechnology, particularly peptide-based nanoparticles (NPs), is increasingly recognized as a valuable strategy to address these obstacles. Peptides provide a versatile platform offering high biocompatibility, specificity, biodegradability, and minimal immunogenicity, making them ideal for targeted cancer therapies. This review comprehensively examines recent advancements in peptide-based nanoparticle systems, highlighting the mechanisms driving peptide self-assembly, such as amphiphilicity, non-covalent interactions, and metal coordination. It distinguishes between non-bioactive peptide nanoparticles, which primarily serve as drug carriers, and bioactive peptide nanoparticles, which integrate targeting peptides, cell-penetrating peptides (CPPs), and therapeutic peptides to enhance specificity, internalization, and anticancer efficacy. Emphasis is placed on innovative designs that exploit active targeting, stimuli-responsive release, and immunomodulatory strategies to maximize therapeutic outcomes while minimizing side effects. Despite promising preclinical outcomes, the clinical translation of peptide nanoparticles struggles with challenges involving stability, delivery efficiency, scalability, regulatory compliance, and manufacturing complexity. The review concludes by outlining future directions, emphasizing personalized nanomedicine, combination therapies, and advanced peptide engineering as crucial pathways toward successful clinical implementation. Full article

(This article belongs to the Special Issue Nanoparticle-Based Drug Delivery in Cancer Therapy: Current Progress and Challenges)

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13 pages, 943 KiB

Open AccessArticle

Prevalence, Evolution and Prognostic Factors of PASC in a Cohort of Patients Discharged from a COVID Unit

by Mariantonietta Pisaturo, Antonio Russo, Pierantonio Grimaldi, Caterina Monari, Simona Imbriani, Klodian Gjeloshi, Carmen Ricozzi, Roberta Astorri, Caterina Curatolo, Roberta Palladino, Francesco Caruso, Francesca Ambrisi, Lorenzo Onorato and Nicola Coppola

Biomedicines 2025, 13(6), 1414; https://doi.org/10.3390/biomedicines13061414 - 9 Jun 2025

Abstract

Background and Aim: PASC is a potentially debilitating clinical condition consisting of different general symptoms experienced by about 10% of patients with previous SARS-CoV-2 infection. Our study analyses a cohort of patients with a history of hospitalization for COVID-19 and aims to [...] Read more.

Background and Aim: PASC is a potentially debilitating clinical condition consisting of different general symptoms experienced by about 10% of patients with previous SARS-CoV-2 infection. Our study analyses a cohort of patients with a history of hospitalization for COVID-19 and aims to evaluate prognostic factors for experiencing PASC and to investigate the characteristics of patients experiencing PASC symptoms. Methods: This is an observational, monocentric retrospective study including all adult patients admitted to our COVID unit from 28 February 2020 to 30 April 2022, discharged alive, and having performed at least one follow-up visit at our post-COVID outpatient clinic after a minimum of three months from discharge. Patients who experienced persistent clinical manifestations or the development of new symptoms three months after the initial SARS-CoV-2 infection, with these symptoms lasting for at least two months with no other explanation, were defined as having PASC. Results: A total of 429 patients were discharged alive from our COVID Unit and 244 patients performed at least one follow-up visit in our outpatient clinic. Of these, 134 patients did not experience PASC, while 110 patients experienced PASC. Long-COVID patients were more frequently female (43.6% vs. 31.3%, p = 0.048), more frequently presented throat pain and headache at hospital admission (respectively 8.9% vs. 2.5%, p = 0.041 and 15.8% vs. 5%, p = 0.007), and were more likely to have a history of type 2 diabetes mellitus (25.5% vs. 13%, p =0.013). At the multivariable analysis, female gender, type 2 diabetes, and headache at admission were factors associated with PASC. All 46 patients who performed at least two different admissions in our outpatient clinic were divided in two groups: the first including the 16 patients who experienced a reduction or a resolution of symptoms related to COVID-19, the second comprising the 30 patients who experienced clinical worsening or persisting symptoms. Smoking habit was more represented among patients with stable or worsening symptoms (42.3% vs. 7.7%, p = 0.042); myalgias at admission were more frequent in the clinical worsening group (27.6% vs. 0%, p= 0.039); and a larger amount of patients who reported neuropsychiatric symptoms and respiratory symptoms were in the stable or worsening PASC symptoms group. Discussion: In conclusion, this study underscores the complexity of PASC, identifying female sex, Type 2 diabetes, and certain acute COVID-19 symptoms as potential predisposing factors for its development. PASC still represents a substantial public health challenge, and ongoing efforts are essential to better understand its underlying mechanisms and improve patient outcomes. Full article

(This article belongs to the Special Issue SARS-CoV-2 Infection: Focus on Pathophysiological Characteristics, Complications and Effects of Vaccinations)

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13 pages, 507 KiB

Open AccessReview

Optimizing Nephron Performance: The Old, the New, and the New–Old Diuretic Therapies

by Flavio D. Fuchs, Guilherme S. Procianoy, Leonardo G. Bottino, Sandra C. Fuchs and Paul K. Whelton

Biomedicines 2025, 13(6), 1413; https://doi.org/10.3390/biomedicines13061413 - 9 Jun 2025

Abstract

Pharmacological influence on nephron function has modified the clinical course of hypertension, heart failure, and chronic kidney disease. (CKD). This is a review of the efficacy of old diuretics and the incremental efficacy of new diuretics in managing hypertension, heart failure, and CKD, [...] Read more.

Pharmacological influence on nephron function has modified the clinical course of hypertension, heart failure, and chronic kidney disease. (CKD). This is a review of the efficacy of old diuretics and the incremental efficacy of new diuretics in managing hypertension, heart failure, and CKD, concluding with new evidence on the effectiveness of old agents. The efficacy of “older” diuretic agents, such as thiazide and loop diuretics, on heart failure and CKD has been primarily explored in nonrandomized studies. However, the efficacy of these agents and indapamide, a slightly newer but still “old” diuretic in preventing blood pressure-related cardiovascular disease, has been demonstrated in randomized controlled trials. Potassium-sparing agents counteract some of the adverse effects of thiazides and have been shown to prevent cardiovascular events in patients with heart failure. Newer drugs with a diuretic effect, such as gliflozins, act through a new mechanism of action in the kidney and have shown efficacy in controlling symptoms and preventing cardiovascular events in patients with heart failure, regardless of diabetes. Furthermore, gliflozins have prevented the progression of chronic kidney disease in patients with and without diabetes mellitus. New evidence detailing the efficacy of old agents has emerged. Chlorthalidone had a large blood-pressure-lowering effect in patients with stage IV CKD. Acetazolamide was effective in accelerating the clinical control of patients with acute heart failure, including patients with some reduction in kidney function. We anticipate investigating the comparative impact of combining different agents to optimize nephron function in the future. Full article

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

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15 pages, 1631 KiB

Open AccessArticle

Altered Expression of NK Receptors in Racially/Ethnically Diverse and Risk-of-Relapse Pediatric Acute Lymphoblastic Leukemia Patients

by Stephen Mathew, Roslin George, Alexsis Garcia, Sheila Powers, Subhash Aryal and W. Paul Bowman

Biomedicines 2025, 13(6), 1412; https://doi.org/10.3390/biomedicines13061412 - 9 Jun 2025

Abstract

Background/Objectives: Acute Lymphoblastic Leukemia (ALL) is a cancer that predominantly affects white blood cells within the blood and bone marrow of adults and children. Currently, ALL is one of the most prevalent malignancies in pediatric patients and is most seen among Caucasian and [...] Read more.

Background/Objectives: Acute Lymphoblastic Leukemia (ALL) is a cancer that predominantly affects white blood cells within the blood and bone marrow of adults and children. Currently, ALL is one of the most prevalent malignancies in pediatric patients and is most seen among Caucasian and Hispanic descent, with lower incidence in African American children. The goal of the study was to investigate the expression of immune cell receptors in racial/ethnic populations and risk factors for relapse that could potentially influence the pediatric ALL outcomes. Methods: Twenty healthy subjects and forty-two pediatric ALL subjects were enrolled in the study and whole-blood was collected at diagnosis and post-chemotherapy, and the cell surface expression of various immune receptors, including 2B4, CS1, LLT1, Nkp30, and NKp46, was determined by flow cytometry. Results: Very high-risk and high-risk of relapse ALL subjects showed increased expression of LLT1 on NK cells, T cells, and monocytes at diagnosis compared to healthy subjects. CS1 was also significantly overexpressed on monocytes of very-high risk ALL subjects both at diagnosis and after the end of chemotherapy as compared to healthy subjects. Also, there was a significantly increased expression of NKp30 on T cells of Caucasians as compared to Hispanics and African Americans at diagnosis, and downregulation of CS1 and LLT1 on T cells of Caucasians post-induction chemotherapy. Conclusions: The altered expression of immune receptors in racial/ethnic and risk stratified groups may provide insights into the immune surveillance mediated by T cells and NK cells against pediatric ALL. Full article

(This article belongs to the Special Issue Advances in Cancer Biology and Experimental Anticancer Therapies (2nd Edition))

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11 pages, 1135 KiB

Open AccessArticle

Pharmacokinetics and Ex Vivo Activity of 7-Methylxanthine, an Inhibitor of Monosodium Urate Crystallization

by Miguel D. Ferrer, Jaume Dietrich, Bernat Isern, Maria del Mar Pérez-Ferrer, Joan Albertí, Félix Grases and Antònia Costa-Bauzà

Biomedicines 2025, 13(6), 1411; https://doi.org/10.3390/biomedicines13061411 - 9 Jun 2025

Abstract

Background/Objectives: 7-Methylxanthine (7-MX) is a naturally occurring metabolite of caffeine and theobromine that can inhibit the crystallization of monosodium urate (MSU) and may be useful for the prevention or treatment of gout. However, the pharmacokinetics and ex vivo activity of 7-MX remain poorly [...] Read more.

Background/Objectives: 7-Methylxanthine (7-MX) is a naturally occurring metabolite of caffeine and theobromine that can inhibit the crystallization of monosodium urate (MSU) and may be useful for the prevention or treatment of gout. However, the pharmacokinetics and ex vivo activity of 7-MX remain poorly characterized. Methods: The present study assessed the pharmacokinetics of 7-MX in Sprague Dawley rats following a single oral dose (30 mg/kg), and the ex vivo inhibition of MSU crystallization by 7-MX in rat plasma after the repeated administration of oral 7-MX. Results: The pharmacokinetic analysis showed that 7-MX reached peak plasma concentration (C_max ≈ 30 µM) at 30 min after administration (t_max), the terminal half-life was approximately 1.4 h, and there was no evidence of accumulation after repeated daily dosing. After repeated administration, the relationship between dose (30 or 60 mg/kg) and plasma concentration was proportional. In vitro and ex vivo crystallization assays demonstrated that 7-MX inhibited MSU crystallization in a concentration-dependent manner. The in vitro studies showed that 100 µM 7-MX inhibited up to 74% of MSU crystallization under supersaturated conditions (400 mg/L urate). The ex vivo experiments indicated that plasma from rats that received 30 or 60 mg/kg of 7-MX had 41.4% and 52.6% inhibition of crystallization, consistent with the measured plasma concentrations. Conclusions: These findings confirm that oral administration of 7-MX to rats led to a plasma level that was sufficient to decrease MSU crystallization in plasma, and there were no observable toxicities. These results support the potential of 7-MX as a safe oral treatment for gout, especially in combination with urate-lowering therapies, such as allopurinol. Further clinical investigations are warranted to confirm the therapeutic potential of 7-MX in humans. Full article

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

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15 pages, 1894 KiB

Open AccessReview

A Comparative Analysis of Radiological Imaging and Surgical Treatments for Maxillary Artery Pseudoaneurysms, Based on a Literature Review and Our Clinical Experience

by Kinga Samól, Adam Michcik, Barbara Wojciechowska, Adam Polcyn, Łukasz Garbacewicz and Barbara Drogoszewska

Biomedicines 2025, 13(6), 1410; https://doi.org/10.3390/biomedicines13061410 - 9 Jun 2025

Abstract

Background/Objectives: A pseudoaneurysm forms as a result of disruption of all artery wall layers. In the head and neck, they are most commonly found in the maxillary artery. Due to their location and associated symptoms, detailed radiological imaging is necessary to determine [...] Read more.

Background/Objectives: A pseudoaneurysm forms as a result of disruption of all artery wall layers. In the head and neck, they are most commonly found in the maxillary artery. Due to their location and associated symptoms, detailed radiological imaging is necessary to determine the nature and extent of lesions. Various treatment methods are available. Methods: To systematize symptoms, diagnostics, and treatment methods, a literature review from databases spanning 2014 to 2024 was conducted, with 30 articles included in the study. Results: The factors that caused MAPs included facial trauma (n = 33; 66%), iatrogenic surgical procedures (n = 14; 28%), head and neck radiotherapy (n = 1; 2%), infection (n = 1; 2%), and one case due to an idiopathic factor (n = 1; 2%). Diagnostic imaging included computed tomography with contrast, magnetic resonance imaging, and angiography. Treatment methods used: endovascular embolization (n = 44; 88%), surgical resection (n = 3; 6%), cauterization (n = 2; 4%), and compression tamponade (n = 1; 2%). Interestingly, three of the cases were treated with endoscopic access (6%). Conclusions: It can be concluded that the most common cause of MAPs is trauma to the facial skeleton, and the most frequently used treatment method is endovascular embolization. Given the need for detailed MAP imaging and treatment in specialized invasive radiology departments, patients with MAPs should be treated in multidisciplinary clinical centers. Full article

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

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22 pages, 3118 KiB

Open AccessReview

Pharmacological and Pathological Implications of Sigma-1 Receptor in Neurodegenerative Diseases

by Noah Drewes, Xiangwei Fang, Nikhil Gupta and Daotai Nie

Biomedicines 2025, 13(6), 1409; https://doi.org/10.3390/biomedicines13061409 - 8 Jun 2025

Abstract

Originally identified as a potential receptor for opioids, the sigma-1 receptor is now recognized as an intracellular chaperone protein associated with mitochondria-associated membranes at the endoplasmic reticulum (ER). Over the past two decades, extensive research has revealed that the sigma-1 receptor regulates many [...] Read more.

Originally identified as a potential receptor for opioids, the sigma-1 receptor is now recognized as an intracellular chaperone protein associated with mitochondria-associated membranes at the endoplasmic reticulum (ER). Over the past two decades, extensive research has revealed that the sigma-1 receptor regulates many cellular processes, such as calcium homeostasis, oxidative stress responses, protein folding, and mitochondrial function. The various functions of the sigma-1 receptor highlight its role as a central modulator of neuronal health and may be a promising pharmacological target across multiple neurodegenerative conditions. Herein, we provide an overview of the current pharmacological understanding of the sigma-1 receptor with an emphasis on the signaling mechanisms involved. We examine its pathological implications in common neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, Huntington’s disease, and multiple sclerosis. We then highlight how sigma-1 receptor modulation may influence disease progression as well as potential pharmacological mechanisms to alter disease outcomes. The translational potential of sigma-1 receptor therapies is discussed, as well as the most up-to-date results of ongoing clinical trials. This review aims to clarify the therapeutic potential of the sigma-1 receptor in neurodegeneration and guide future research in these diseases. Full article

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

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23 pages, 11326 KiB

Open AccessArticle

Pharmacological Evaluation of Araliadiol as a Novel Anti-Inflammatory Agent in LPS-Induced RAW 264.7 Cells

by Seokmuk Park, Suhyeon Cho, Hee-Jae Shin, Seyeol Baek, Hye-In Gwon, Jungmin Lee, Dae Sung Yoo, Han Woong Park, Dae Bang Seo and Seunghee Bae

Biomedicines 2025, 13(6), 1408; https://doi.org/10.3390/biomedicines13061408 - 8 Jun 2025

Abstract

Background/Objectives:Inflammatory disorders contribute to the pathogenesis of numerous diseases and are known to markedly reduce quality of life. Although anti-inflammatory drugs approved by the Food and Drug Administration are available, their prolonged use is frequently associated with adverse effects. In this study, [...] Read more.

Background/Objectives:Inflammatory disorders contribute to the pathogenesis of numerous diseases and are known to markedly reduce quality of life. Although anti-inflammatory drugs approved by the Food and Drug Administration are available, their prolonged use is frequently associated with adverse effects. In this study, we evaluated the pharmacological properties of araliadiol, a naturally occurring polyacetylene compound, as a novel anti-inflammatory agent. Methods: An in vitro hyperinflammatory model was established by stimulating RAW 264.7 cells with lipopolysaccharide (LPS). Dexamethasone (DEX) was used as a positive control to compare anti-inflammatory efficacy. The protective effects of araliadiol against LPS-induced cytotoxicity were assessed using adenosine triphosphate content and crystal violet staining assays. The anti-inflammatory activity was further examined by quantitative reverse transcriptase–polymerase chain reaction, Western blotting, cell fractionation, immunofluorescence staining, a nitric oxide assay, and an enzyme-linked immunosorbent assay. Results: Araliadiol significantly attenuated cytotoxicity and cell death in LPS-stimulated RAW 264.7 cells. It suppressed the expression of cell death markers Cleaved caspase-3 and Cleaved PARP-1. In addition, araliadiol downregulated key pro-inflammatory mediators, including inflammasome-related genes, cytokines, chemokines, and inducible nitric oxide synthase. It also reduced the expression of Cox-2 and PGE₂, indicating potential anti-hyperalgesic effects. Moreover, araliadiol inhibited the activation of Nfκb and Stat1 signaling pathways in LPS-stimulated macrophages. Conclusions: Araliadiol demonstrated robust anti-cytotoxic, anti-inflammatory, and anti-hyperalgesic activities in LPS-induced RAW 264.7 cells, with efficacy comparable to DEX. These findings support its potential as a plant-derived therapeutic candidate for the management of inflammatory conditions. Full article

(This article belongs to the Special Issue Exploring Potential Therapeutic Compounds with Anti-Inflammatory Activity)

12 pages, 305 KiB

Open AccessArticle

Real-World Effectiveness of Different Nutraceutical Formulations on Pain Intensity of Subjects with Diabetic Peripheral Neuropathy: An Observational, Retrospective, Case–Control Study

by Laura Armeli Grigio, Denisa Boci, Giacoma Di Vieste, Gianluca Cassanelli, Oscar Massimiano Epis, Alessandro Viadana, Federico Bertuzzi and Basilio Pintaudi

Biomedicines 2025, 13(6), 1407; https://doi.org/10.3390/biomedicines13061407 - 8 Jun 2025

Abstract

Background/Objectives. Diabetic peripheral neuropathy is a debilitating disease-related complication with a significant impact on quality of life. Its management represents a therapeutic challenge. Antioxidant agents such as α-lipoic acid, N-acetyl cysteine, and glutatione may be useful treatment strategies. Methods. A real-world, [...] Read more.

Background/Objectives. Diabetic peripheral neuropathy is a debilitating disease-related complication with a significant impact on quality of life. Its management represents a therapeutic challenge. Antioxidant agents such as α-lipoic acid, N-acetyl cysteine, and glutatione may be useful treatment strategies. Methods. A real-world, observational, retrospective, case–control study involving consecutive subjects with type 2 diabetes with diabetic peripheral neuropathy was performed. Participants who were supplemented with three different formulations for 12 weeks (high-dose α-lipoic acid (800 mg); low-dose α-lipoic acid (100 mg) plus glutathione (200 mg) plus Vitamin D (800 IU); N-acetyl cysteine (600 mg) plus glutathione (200 mg) plus Vitamin D (800 IU)) were compared with a non-treated control group. Questionnaires aimed at investigating the degree of disability and quality of life were administered. The primary endpoint was the change in neuropathic pain intensity measured by the Numerical Rating Scale (NRS). Results. Among 750 consecutive screened subjects with type 2 diabetes, 98 (13%) had diabetic neuropathy (mean age 66.7 ± 7.6 years, diabetes duration 11.3 ± 6.7 years, HbA1c 8.1 ± 1.5%, 43.8% insulin-treated). When comparing the differences between treatment groups in the changes in individual questionnaire scores between baseline and follow-up, all three supplements showed significant reductions compared to the control group in the NRS scale scores. No side effects have been reported during the study. Conclusions. As well as lipoic acid, other substances with specific activity on the genesis of neuropathic pain, such as N-acetyl cysteine and glutathione, have proved effective in reducing the intensity of pain. Full article

(This article belongs to the Special Issue Novel Biomarker and Treatments for Diabetic Neuropathy)

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44 pages, 891 KiB

Open AccessReview

Aquaporins in Acute Brain Injury: Insights from Clinical and Experimental Studies

by Stelios Kokkoris, Charikleia S. Vrettou, Nikolaos S. Lotsios, Vasileios Issaris, Chrysi Keskinidou, Kostas A. Papavassiliou, Athanasios G. Papavassiliou, Anastasia Kotanidou, Ioanna Dimopoulou and Alice G. Vassiliou

Biomedicines 2025, 13(6), 1406; https://doi.org/10.3390/biomedicines13061406 - 7 Jun 2025

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Abstract

Aquaporins (AQPs) are a family of transmembrane water channel proteins facilitating the transport of water and, in some cases, small solutes such as glycerol, lactate, and urea. In the central nervous system (CNS), several aquaporins play crucial roles in maintaining water homeostasis, modulating [...] Read more.

Aquaporins (AQPs) are a family of transmembrane water channel proteins facilitating the transport of water and, in some cases, small solutes such as glycerol, lactate, and urea. In the central nervous system (CNS), several aquaporins play crucial roles in maintaining water homeostasis, modulating cerebrospinal fluid (CSF) circulation, regulating energy metabolism, and facilitating neuroprotection under pathological conditions. Among them, AQP2, AQP4, AQP9, and AQP11 have been implicated in traumatic and non-traumatic brain injuries. The most abundant aquaporin (AQP) in the brain, AQP4, is essential for fluid regulation, facilitating water transport across the blood–brain barrier and glymphatic clearance. AQP2 is primarily known for its function in the kidneys, but it is also expressed in brain regions related to vasopressin signaling and CSF dynamics. AQP9 acts as a channel for glycerol and lactate, thus playing a role in metabolic adaptation during brain injury. AQP11, an intracellular aquaporin, is involved in oxidative stress responses and cellular homeostasis, with emerging evidence suggesting its role in neuroprotection. Aquaporins play a dual role in brain injury; while they help maintain homeostasis, their dysregulation can exacerbate cerebral edema, metabolic dysfunction, and inflammation. In traumatic brain injury (TBI), aquaporins regulate the formation and resolution of cerebral edema. In non-traumatic brain injuries, including ischemic stroke, aneurysmal subarachnoid hemorrhage (aSAH), and intracerebral hemorrhage (ICH), aquaporins influence fluid balance, energy metabolism, and oxidative stress responses. Understanding the specific roles of AQP2, AQP4, AQP9, and AQP11 in these brain injuries may lead to new therapeutic strategies to mitigate secondary damage and improve neurological outcomes. This review explores the function of the above aquaporins in both traumatic and non-traumatic brain injuries, highlighting their potential and limitations as therapeutic targets for neuroprotection and recovery. Full article

(This article belongs to the Special Issue Brain Injury: New Insights into Mechanisms and Future Promising Treatments—Second Edition)

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13 pages, 401 KiB

Open AccessArticle

MAPT Subhaplotypes in Different Progressive Supranuclear Palsy Phenotypes

by Monica Gagliardi, Radha Procopio, Alessia Felicetti, Grazia Annesi, Mariagrazia Talarico, Basilio Vescio, Aldo Quattrone and Andrea Quattrone

Biomedicines 2025, 13(6), 1405; https://doi.org/10.3390/biomedicines13061405 - 7 Jun 2025

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Abstract

Background: Progressive Supranuclear Palsy (PSP) is a rare neurodegenerative disorder characterized by abnormal tau protein aggregation. The MAPT gene encodes for tau protein. The MAPT locus harbors two major haplotypes, H1 and H2, with H1 and its subhaplotypes being associated with an increased [...] Read more.

Background: Progressive Supranuclear Palsy (PSP) is a rare neurodegenerative disorder characterized by abnormal tau protein aggregation. The MAPT gene encodes for tau protein. The MAPT locus harbors two major haplotypes, H1 and H2, with H1 and its subhaplotypes being associated with an increased risk of PSP. Methods: In this study, we genotyped rs8070723 in a cohort of 73 PSP patients, including 47 PSP Richardson Syndrome (PSP-RS) and 27 PSP variants (vPSP), and 93 age-matched healthy controls (HC) from Southern Italy. Results: Haplotype analysis identified H1 and H2 haplotypes that conferred a risk (OR, 2.620; 95% CI, 1.399–5.140; p = 0.0035) and a protective effect (OR, 0.370; 95% CI, 0.196–0.695; p = 0.0015), respectively. In addition, we genotyped five MAPT variants (rs1467967, rs242557, rs3785883, rs2471738, and rs7521) that, together with rs8070723, defined H1 subhaplotypes. We identified 18 distinct MAPT H1 subhaplotypes, among which H1j displayed a nominally significant reduced risk of PSP (OR, 0.201; 95% CI, 0.044–0.915; p = 0.0265). Conclusions: These findings reinforce the role of MAPT genetic variation in PSP pathogenesis and highlight the potential impact of haplotype diversity on disease susceptibility. Full article

(This article belongs to the Section Gene and Cell Therapy)

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17 pages, 401 KiB

Open AccessReview

The Impact of Radioiodine (131I) Therapy of Thyroid Disease on Salivary Glands Function and Inflammation: A Comprehensive Review

by Pietro Bellini, Francesco Dondi, Carlo Cappelli, Elisa Gatta, Davide Lombardi, Claudio Casella, Riccardo Morandi, Gianluca Viganò, Luca Camoni, Michela Cossandi, Valentina Zilioli and Francesco Bertagna

Biomedicines 2025, 13(6), 1404; https://doi.org/10.3390/biomedicines13061404 - 7 Jun 2025

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Abstract

Radioactive iodine therapy has been a well-established treatment for various thyroid conditions since the 1940s, targeting both benign diseases and malignancies. Treatment for benign conditions typically involves low doses of 131I, often requiring no more than two treatments, with the dose either fixed [...] Read more.

Radioactive iodine therapy has been a well-established treatment for various thyroid conditions since the 1940s, targeting both benign diseases and malignancies. Treatment for benign conditions typically involves low doses of 131I, often requiring no more than two treatments, with the dose either fixed or personalized based on thyroid tissue mass and iodine uptake. In contrast, differentiated thyroid cancer treatment often requires higher doses and multiple administrations, especially for metastatic cases. Recent guidelines and studies have proposed more conservative management strategies, including careful follow-up, due to concerns over the high risk–benefit ratio in selected cases with a low risk of disease recrudescence. Despite its possible efficacy, radioiodine therapy is associated with dose-dependent side effects, the most common of which is salivary gland dysfunction or inflammation, affecting approximately 30% of adult patients. These effects pose significant challenges in nuclear medicine practice. This review aims to summarize the latest evidence on the incidence, impact on quality of life, prevention strategies and the role of these side effects in the decision-making process regarding RAI therapy. Full article

(This article belongs to the Special Issue Thyroid Disease: From Mechanism to Therapeutic Approaches)

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5 pages, 458 KiB

Open AccessEditorial

10th Anniversary of Biomedicines—Advances in Endothelial Dysfunction

by Francesca Schinzari, Carmine Cardillo and Manfredi Tesauro

Biomedicines 2025, 13(6), 1403; https://doi.org/10.3390/biomedicines13061403 - 7 Jun 2025

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Abstract

The vascular endothelium serves as an essential interface between tissues and the bloodstream, playing a key role in the regulation of blood flow [...] Full article

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

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