Journal Description
Biomedicines
Biomedicines
is an international, peer-reviewed, open access journal on biomedicines published monthly online by MDPI.
- Open Access— free for readers, with article processing charges (APC) paid by authors or their institutions.
- High Visibility: indexed within Scopus, SCIE (Web of Science), PubMed, PMC, CAPlus / SciFinder, and other databases.
- Journal Rank: JCR - Q1 (Pharmacology and Pharmacy) / CiteScore - Q2 (Medicine (miscellaneous))
- Rapid Publication: manuscripts are peer-reviewed and a first decision is provided to authors approximately 14.6 days after submission; acceptance to publication is undertaken in 2.8 days (median values for papers published in this journal in the second half of 2024).
- Recognition of Reviewers: reviewers who provide timely, thorough peer-review reports receive vouchers entitling them to a discount on the APC of their next publication in any MDPI journal, in appreciation of the work done.
- Companion journals for Biomedicines include: IJTM, BioMed, Anesthesia Research and Emergency Care and Medicine.
Impact Factor:
3.9 (2023);
5-Year Impact Factor:
4.1 (2023)
Latest Articles
A CECT-Based Radiomics Nomogram Predicts the Overall Survival of Patients with Hepatocellular Carcinoma After Surgical Resection
Biomedicines 2025, 13(5), 1237; https://doi.org/10.3390/biomedicines13051237 (registering DOI) - 19 May 2025
Abstract
Objective: The primary objective of this study was to develop and validate a predictive nomogram that integrates radiomic features derived from contrast-enhanced computed tomography (CECT) images with clinical variables to predict overall survival (OS) in patients with hepatocellular carcinoma (HCC) after surgical
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Objective: The primary objective of this study was to develop and validate a predictive nomogram that integrates radiomic features derived from contrast-enhanced computed tomography (CECT) images with clinical variables to predict overall survival (OS) in patients with hepatocellular carcinoma (HCC) after surgical resection. Methods: This retrospective study analyzed the preoperative enhanced CT images and clinical data of 202 patients with HCC who underwent surgical resection at the Affiliated Hospital of North Sichuan Medical College (Institution 1) from June 2017 to June 2021 and at Nanchong Central Hospital (Institution 2) from June 2020 to June 2022. Among these patients, 162 patients from Institution 1 were randomly divided into a training cohort (112 patients) and an internal validation cohort (50 patients) at a 7:3 ratio, whereas 40 patients from Institution 2 were assigned as an independent external validation cohort. Univariate and multivariate Cox proportional hazards regression analyses were performed to identify clinical risk factors associated with OS after HCC resection. Using 3D-Slicer software, tumor lesions were manually delineated slice by slice on preoperative non-contrast-enhanced (NCE) CT, arterial phase (AP), and portal venous phase (PVP) images to generate volumetric regions of interest (VOIs). Radiomic features were subsequently extracted from these VOIs. LASSO Cox regression analysis was employed for dimensionality reduction and feature selection, culminating in the construction of a radiomic signature (Radscore). Cox proportional hazards regression models, including a clinical model, a radiomic model, and a radiomic–clinical model, were subsequently developed for OS prediction. The predictive performance of these models was assessed via the concordance index (C-index) and time–ROC curves. The optimal performance model was further visualized as a nomogram, and its predictive accuracy was evaluated via calibration curves and decision curve analysis (DCA). Finally, the risk factors in the optimal performance model were interpreted via Shapley additive explanations (SHAP). Results: Univariate and multivariate Cox regression analyses revealed that BCLC stage, the albumin–bilirubin index (ALBI), and the NLR–PLR score were independent predictors of OS after HCC resection. Among these three models, the radiomic–clinical model exhibited the highest predictive performance, with C-indices of 0.789, 0.726, and 0.764 in the training, internal and external validation cohorts, respectively. Furthermore, the time–ROC curves for the radiomic–clinical model showed 1-year and 3-year AUCs of 0.837 and 0.845 in the training cohort, 0.801 and 0.880 in the internal validation cohort, and 0.773 and 0.840 in the external validation cohort. Calibration curves and DCA demonstrated the model’s excellent calibration and clinical applicability. Conclusions: The nomogram combining CECT radiomic features and clinical variables provides an accurate prediction of OS after HCC resection. This model is beneficial for clinicians in developing individualized treatment strategies for patients with HCC.
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(This article belongs to the Special Issue New Insights into the Diagnosis and Treatment of Hepatocellular Carcinoma)
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Prevalence of Viral and Bacterial Co-Infections in SARS-CoV-2-Positive Individuals in Cyprus 2020–2022
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George Krashias, Christina Tryfonos, Stavros Bashiardes, Jan Richter and Christina Christodoulou
Biomedicines 2025, 13(5), 1236; https://doi.org/10.3390/biomedicines13051236 (registering DOI) - 19 May 2025
Abstract
The COVID-19 pandemic has had a profound impact on healthcare systems worldwide, with severe consequences on the global economy and society. The clinical presentation of SARS-CoV-2 infection varies widely, ranging from asymptomatic cases to severe disease and death. Coinfection with other respiratory pathogens
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The COVID-19 pandemic has had a profound impact on healthcare systems worldwide, with severe consequences on the global economy and society. The clinical presentation of SARS-CoV-2 infection varies widely, ranging from asymptomatic cases to severe disease and death. Coinfection with other respiratory pathogens in SARS-CoV-2-positive individuals may exacerbate symptom severity and lead to poorer clinical outcomes. Background/Objectives: This study is the first to investigate the prevalence of viral and bacterial co-infections in SARS-CoV-2-positive individuals in Cyprus. Methods: A total of 1111 SARS-CoV-2-positive nasopharyngeal swab samples collected from non-hospitalized patients were analyzed for the presence of 18 viral and 3 bacterial respiratory pathogens. Results: Of these, 51 samples (4.6%) were found to have at least one additional respiratory pathogen. The most frequently detected viruses were rhinovirus/enterovirus (n = 28; 2.5%) and adenovirus (n = 8; 0.7%), while the bacterial pathogens identified were Legionella pneumophila (n = 1; 0.1%) and Bordetella pertussis (n = 1; 0.1%). The highest proportion of co-infections was observed in the youngest age group (<10 years), where 52.9% of co-infections were identified, followed by the 30–39 age group, which accounted for 15.7% of cases. Among single respiratory virus co-infections, rhinovirus/enterovirus (27.5%) and adenovirus (13.7%) were the most frequently detected in the <10 age group, followed by RSV (3.9%), bocavirus, influenza B, HMPV A + B, and coronavirus NL63 (each at 2%). Conclusions: The current study underscores the importance of simultaneous testing for SARS-CoV-2 and other respiratory pathogens, as this may have significant implications for both individual patient care and healthcare services.
Full article
(This article belongs to the Special Issue Advanced Biomedical Research on COVID-19 (2nd Edition))
Open AccessArticle
Predictive Accuracy of a Clinical Model for Carriage of Pathogenic/Likely Pathogenic Variants in Patients with Dementia and a Positive Family History at PUMCH
by
Jialu Bao, Yuyue Qiu, Tianyi Wang, Li Shang, Shanshan Chu, Wei Jin, Wenjun Wang, Yuhan Jiang, Bo Li, Yixuan Huang, Bo Hou, Longze Sha, Yunfan You, Yuanheng Li, Meiqi Wu, Yutong Zou, Yifei Wang, Li Huo, Ling Qiu, Qi Xu, Feng Feng, Chenhui Mao, Liling Dong and Jing Gaoadd
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Biomedicines 2025, 13(5), 1235; https://doi.org/10.3390/biomedicines13051235 (registering DOI) - 19 May 2025
Abstract
Background and Objectives: Identifying carriers of Pathogenic/Likely Pathogenic Variants in patients with dementia is crucial for risk stratification, particularly in individuals with a family history. This study developed and validated a clinical prediction model using whole-exome sequencing-confirmed cohorts. Methods: A total of 601
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Background and Objectives: Identifying carriers of Pathogenic/Likely Pathogenic Variants in patients with dementia is crucial for risk stratification, particularly in individuals with a family history. This study developed and validated a clinical prediction model using whole-exome sequencing-confirmed cohorts. Methods: A total of 601 Chinese patients with dementia and a family history were enrolled at Peking Union Medical College Hospital, with 476 in a retrospective derivation cohort and 125 in a temporal validation cohort. Predictive factors included age at onset, APOE ε4 status, and family history characteristics. Model performance was assessed using discrimination and calibration metrics. Results: In the derivation cohort (median age at onset 66 years), 10.3% carried Pathogenic/Likely Pathogenic Variants. Among patients with dementia, those with age at onset < 55 years (OR 2.56, p = 0.0098), more than two affected relatives (OR 3.32, p = 0.0039), parental disease history (OR 4.72, p = 0.015), and early-onset cases in the family (OR 2.61, p = 0.0096) were positively associated with Pathogenic/Likely Pathogenic Variant carriage, whereas APOE ε4 carriage was inversely associated (OR 0.36, p = 0.0041). The model achieved an area under the curve of 0.776 (95% CI, 0.701–0.853) in the derivation cohort and 0.781 (95% CI, 0.647–0.914) in the validation cohort (median age at onset 58 years), with adequate calibration. Conclusions: This model demonstrated strong predictive performance for Pathogenic/Likely Pathogenic Variant carriage, supporting its clinical utility in guiding genetic testing. Further research is needed to refine the model.
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(This article belongs to the Special Issue Neurodegeneration in Cognitive Impairment and Mood Disorders for Experimental, Clinical, and Translational Neuropsychiatry—Second Edition)
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Dual Inhibition of HIF-1α and HIF-2α as a Promising Treatment for VHL-Associated Hemangioblastomas: A Pilot Study Using Patient-Derived Primary Cell Cultures
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Ana B. Perona-Moratalla, Blanca Carrión, Karina Villar Gómez de las Heras, Lourdes Arias-Salazar, Blanca Yélamos-Sanz, Tomás Segura and Gemma Serrano-Heras
Biomedicines 2025, 13(5), 1234; https://doi.org/10.3390/biomedicines13051234 (registering DOI) - 19 May 2025
Abstract
Background: Von Hippel-Lindau (VHL) disease, a hereditary cancer syndrome, is characterized by mutations in the VHL gene, which result in the stabilization of hypoxia-inducible factors (HIF)-1α and -2α, ultimately leading to the development of highly vascularized tumors, such as hemangioblastomas of the central
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Background: Von Hippel-Lindau (VHL) disease, a hereditary cancer syndrome, is characterized by mutations in the VHL gene, which result in the stabilization of hypoxia-inducible factors (HIF)-1α and -2α, ultimately leading to the development of highly vascularized tumors, such as hemangioblastomas of the central nervous system (CNS-HBs). The standard treatment for these brain tumors is neurosurgical resection. However, multiple surgeries are often necessary due to tumor recurrence, which increases the risk of neurological sequelae. Thus, elucidation of the proliferative behavior of hemangioblastomas (with the aim of identifying biomarkers associated with tumor progression) and the development of pharmacological therapies could reduce the need for repeated surgical interventions and provide alternative treatment options for unresectable CNS-HBs. Belzutifan (Welireg™), a selective HIF-2α inhibitor and the only FDA-approved non-surgical option, has shown limited efficacy in CNS-HBs, highlighting the need for alternative therapeutic strategies. Results: In this study, primary cell cultures were successfully established from CNS-HB tissue samples of VHL patients, achieving a 75% success rate. These cultures were predominantly composed of stromal cells and pericytes. The proliferative patterns of patient-derived HB cell cultures significantly correlated with tumor burden and recurrence in VHL patients. Furthermore, flow cytometry, reverse transcription-PCR, and Western blot analyses revealed marked overexpression of both HIF-1α and HIF-2α isoforms in primary HB cells. In addition, evaluation of the therapeutic potential of acriflavine, a dual HIF-1α/HIF-2α inhibitor, demonstrated reduced HB cells viability, induced G2/M cell cycle arrest, and predominantly triggered necrotic cell death in patient-derived HB cultures. Conclusions: These results suggest that the in vitro proliferative dynamics of HB cell cultures may reflect clinical characteristics associated with CNS-HB progression, potentially serving as indicators to predict tumor development in patients with VHL. Furthermore, our findings support the simultaneous targeting of both HIF-1α and HIF-2α isoforms as a promising non-invasive therapeutic strategy.
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(This article belongs to the Special Issue New Insights in Hypoxic Response Modulation)
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Vitamin D Imbalance and Hydro-Electrolyte Disturbances in Hospitalized Children: A Comparation Between Post-COVID-19 Status and SARS-CoV-2/EBV Coinfection
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Carmen Loredana Petrea (Cliveți), Diana-Andreea Ciortea, Gabriela Gurău, Nicoleta Mădălina Matei, Ciprian Adrian Dinu, Simona-Elena Bergheș (Oprea), Gabriela Isabela Verga (Răuță) and Sorin Ion Berbece
Biomedicines 2025, 13(5), 1233; https://doi.org/10.3390/biomedicines13051233 - 19 May 2025
Abstract
Background/Objectives: SARS-CoV-2 infection has the potential to cause multi-organ involvement and, when associated with Epstein–Barr virus (EBV) coinfection, may worsen the course of disease in pediatric patients by influencing the immune response. Methods: Our retrospective–observational study included 406 hospitalized children with post-COVID-19 status
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Background/Objectives: SARS-CoV-2 infection has the potential to cause multi-organ involvement and, when associated with Epstein–Barr virus (EBV) coinfection, may worsen the course of disease in pediatric patients by influencing the immune response. Methods: Our retrospective–observational study included 406 hospitalized children with post-COVID-19 status or SARS-CoV-2/EBV coinfection. Results: Hypovitaminosis D was more common in the coinfected sublot (59.18%) than in the COVID-19 one (50.74%), with a higher frequency of severe vitamin D deficiency (16.33% vs. 7.35%). Hypovitaminosis D was significantly associated with female sex (p = 0.033) only in the COVID-19 subgroup. Hypervitaminosis D, although rare, was only associated with severe forms of the disease (7.69%). Between clinical severity and vitamin D level, a statistically significant association of moderate intensity was identified only in the COVID-19 subgroup (χ2 = 11.708, φ = 0.293, p = 0.020). In the same subgroup, a significant correlation was found between vitamin D levels and serum potassium values (χ2 = 10.527, p = 0.032). Moreover, in the COVID-19 subgroup, an association between abnormal sodium levels and increased D-dimer levels was found (χ2 = 7.074, p = 0.029). Conclusions: These results underline the importance of monitoring immunologic, vitamin, and electrolyte imbalance in the management of these cases and highlight the need for personalized therapeutic strategies to prevent long-term complications.
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(This article belongs to the Section Cell Biology and Pathology)
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Optimizing Biologic Therapy for the Prevention of Post-Operative Recurrence in Crohn’s Disease: Current Evidence and Future Perspectives
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Reem Aljabri, Saqer Al-Saraie and Ahmed Alhouti
Biomedicines 2025, 13(5), 1232; https://doi.org/10.3390/biomedicines13051232 - 19 May 2025
Abstract
Crohn’s disease (CD) imposes a substantial burden on patients due to its chronic, relapsing nature, often necessitating surgical intervention. However, surgery is not curative, and post-operative recurrence (POR) remains a major clinical challenge, with up to 80% of patients developing endoscopic recurrence within
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Crohn’s disease (CD) imposes a substantial burden on patients due to its chronic, relapsing nature, often necessitating surgical intervention. However, surgery is not curative, and post-operative recurrence (POR) remains a major clinical challenge, with up to 80% of patients developing endoscopic recurrence within one year if left untreated. The pathophysiology of POR is multifactorial, involving dysregulated immune responses, gut microbiota alterations, and mucosal healing impairment, highlighting the need for targeted therapeutic strategies. This review aims to explore the current landscape of POR management, focusing on biologic therapies and emerging advanced treatments. Conventional management relies on early prophylactic therapy with anti-TNF agents such as infliximab and adalimumab, which have demonstrated efficacy in reducing endoscopic and clinical recurrence. However, newer biologics, including IL-23 inhibitors (risankizumab) and Janus kinase (JAK) inhibitors (upadacitinib), have shown promise in CD management, though their role in POR remains underexplored. The lack of direct clinical evidence for advanced biologics in POR prevention, combined with inter-individual variability in treatment response, underscores the need for further research. Future directions should focus on optimizing therapeutic strategies through personalized medicine, identifying predictive biomarkers, and conducting robust trials to establish the efficacy of novel agents in POR prevention. A tailored, evidence-driven approach is essential to improving long-term outcomes and minimizing disease recurrence in post-operative CD patients.
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(This article belongs to the Special Issue Crohn’s Disease and Ulcerative Colitis: From Pathophysiology to Novel Therapeutic Approaches (3rd Edition))
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A Cross-Tissue Transcriptome-Wide Association Study Reveals Novel Susceptibility Genes for Diabetic Kidney Disease in the FinnGen Cohort
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Menghan Liu, Zehua Li, Yao Lu, Pingping Sun, Ying Chen and Li Yang
Biomedicines 2025, 13(5), 1231; https://doi.org/10.3390/biomedicines13051231 - 19 May 2025
Abstract
Background/Objectives: Diabetic kidney disease (DKD) is a common diabetic complication, driven by a multifactorial pathogenesis that includes various genetic components. However, the precise causative genes and their underlying biological pathways remain poorly understood. Methods: We performed a cross-tissue transcriptome-wide association study
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Background/Objectives: Diabetic kidney disease (DKD) is a common diabetic complication, driven by a multifactorial pathogenesis that includes various genetic components. However, the precise causative genes and their underlying biological pathways remain poorly understood. Methods: We performed a cross-tissue transcriptome-wide association study (TWAS) of DKD using expression quantitative trait loci (eQTL) data from 49 tissues in the Genotype—Tissue Expression (GTEx) version 8 (v8) resource. Five complementary analytical frameworks—sparse canonical correlation analysis (sCCA), functional summary-based imputation (FUSION), fine-mapping of causal gene sets (FOCUS), summary-data-based Mendelian randomization (SMR), and multi-marker analysis of genomic annotation (MAGMA)—were integrated to nominate candidate genes. Causal inference was refined using Mendelian randomization (MR), and biological significance was evaluated through pathway enrichment, protein interaction networks, and druggability profiling. Results: We identified 23 candidate genes associated with DKD risk, of which 13 were supported by MR analysis. Among these, 10 represent previously unreported susceptibility genes. Notably, four genes—HLA-DRB1, HLA-DRB5, NOTCH4, and CYP21A2—encode potentially druggable proteins, with HLA-DRB5 and CYP21A2 both qualifying as novel susceptibility genes and therapeutic targets. These genes converge on immune modulation, steroid biosynthesis, DNA repair, and transcriptional regulation—processes central to DKD pathogenesis. Conclusions: Our study represents the first systematic cross-tissue TWAS of DKD, revealing a prioritized set of genetically and functionally supported susceptibility genes. The identification of druggable targets among these genes provides critical insight into the mechanistic underpinnings of DKD and highlights their potential for future therapeutic development. These findings enhance our understanding of DKD pathophysiology and offer a foundation for precision medicine strategies in nephrology.
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(This article belongs to the Section Endocrinology and Metabolism Research)
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Cardiac Amyloidosis: A Narrative Review of Diagnostic Advances and Emerging Therapies
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Dana Emilia Movila, Alexandru Catalin Motofelea, Dragos Cozma, Oana Albai, Alexandra Christa Sima, Minodora Andor, Tudor Ciocarlie and Simona Ruxanda Dragan
Biomedicines 2025, 13(5), 1230; https://doi.org/10.3390/biomedicines13051230 - 19 May 2025
Abstract
Background/Objectives: Cardiac amyloidosis (CA) is an underdiagnosed and potentially life-threatening infiltrative cardiomyopathy characterized by the extracellular deposition of misfolded amyloid fibrils in cardiac tissue. It is most commonly associated with light-chain (AL) amyloidosis and transthyretin (ATTR) amyloidosis, either hereditary or wild-type. The
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Background/Objectives: Cardiac amyloidosis (CA) is an underdiagnosed and potentially life-threatening infiltrative cardiomyopathy characterized by the extracellular deposition of misfolded amyloid fibrils in cardiac tissue. It is most commonly associated with light-chain (AL) amyloidosis and transthyretin (ATTR) amyloidosis, either hereditary or wild-type. The disease often presents with non-specific symptoms, leading to delayed diagnosis and treatment. This study aims to provide a comprehensive overview of the pathophysiology, diagnostic strategies, and current therapeutic approaches for cardiac amyloidosis, with a focus on improving early detection and clinical outcomes. Methods: A narrative review was conducted using databases such as PubMed and Scopus, covering the period from September 2016 to March 2025. Keywords such as “cardiac amyloidosis”, “cardiac amyloidosis from transthyretin”, “cardiomyopathy”, “transthyretin”, “immunoglobulin light-chain amyloidosis”, and “familial amyloidosis” were used. Relevant clinical trials and guideline-based management recommendations were also included. Results: This review highlights that non-invasive imaging modalities and serum biomarker analyses are key to reducing diagnostic delays. New therapeutic developments, including gene-editing technologies and RNA-based therapies, show promise in early trials. Multidisciplinary management and increased awareness are crucial for timely diagnosis and treatment optimization. Conclusions: The early recognition of cardiac amyloidosis remains a major clinical challenge. Advances in non-invasive diagnostics and emerging disease-modifying therapies are transforming the prognosis of affected patients. Continued research and heightened clinical suspicion are essential to improve outcomes in this complex and heterogeneous disease.
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(This article belongs to the Section Molecular and Translational Medicine)
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Exosome Therapy in Stress Urinary Incontinence: A Comprehensive Literature Review
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Manouchehr Nasrollahzadeh Saravi, Mahdi Mohseni, Iman Menbari Oskouie, Jafar Razavi, Ernesto Delgado Cidranes and Masoumeh Majidi Zolbin
Biomedicines 2025, 13(5), 1229; https://doi.org/10.3390/biomedicines13051229 - 19 May 2025
Abstract
Stress urinary incontinence (SUI) is characterized by the involuntary leakage of urine when bladder pressure exceeds urethral closing pressure during routine activities such as physical exertion, coughing, exercise, or sneezing. SUI is the most prevalent form of urinary incontinence, with a reported prevalence
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Stress urinary incontinence (SUI) is characterized by the involuntary leakage of urine when bladder pressure exceeds urethral closing pressure during routine activities such as physical exertion, coughing, exercise, or sneezing. SUI is the most prevalent form of urinary incontinence, with a reported prevalence ranging from 10% to 70%, and its incidence increases with age. As the global population continues to age, the prevalence and clinical significance of SUI are expected to rise accordingly. The pathophysiology of SUI is primarily driven by two mechanisms: urethral hypermobility, resulting from compromised supporting structures, and intrinsic urethral sphincter deficiency, characterized by the deterioration of urethral mucosa and muscle tone. Current treatment options for SUI include conservative management strategies, which heavily rely on patient adherence and are associated with high recurrence rates, and surgical interventions, such as sling procedures, which offer effective solutions but are costly and carry the risk of adverse side effects. These limitations highlight the urgent need for more effective and comprehensive treatment modalities. Exosomes, nano-sized (30–150 nm) extracellular vesicles secreted by nearly all cell types, have emerged as a novel therapeutic option due to their regenerative, anti-fibrotic, pro-angiogenic, anti-apoptotic, anti-inflammatory, and anti-hypoxic properties. These biological functions position exosomes as a promising alternative to conventional therapies for SUI. Exosome therapy has the potential to enhance tissue regeneration, restore urethral function, and repair nerve and muscle damage, thereby reducing symptom burden and improving patients’ quality of life. Additionally, exosome-based treatments could offer a less invasive alternative to surgery, potentially decreasing the need for repeated interventions and minimizing complications associated with current procedures. In this literature review, we critically assess the current state of research on the potential use of exosomes in treating SUI, highlighting their therapeutic mechanisms and potential clinical benefits.
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(This article belongs to the Section Molecular and Translational Medicine)
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Pushing the Limits of Interlimb Connectivity: Neuromodulation and Beyond
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Jane A. Porter, Trevor S. Barss, Darren J. Mann, Zahra Karamzadeh, Deborah O. Okusanya, Sisuri G. Hemakumara, E. Paul Zehr, Taryn Klarner and Vivian K. Mushahwar
Biomedicines 2025, 13(5), 1228; https://doi.org/10.3390/biomedicines13051228 - 19 May 2025
Abstract
The ability to walk is often lost after neural injury, leading to multiple secondary complications that reduce quality of life and increase healthcare costs. The current rehabilitation interventions primarily focus on restoring leg movements through intensive training on a treadmill or using robotic
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The ability to walk is often lost after neural injury, leading to multiple secondary complications that reduce quality of life and increase healthcare costs. The current rehabilitation interventions primarily focus on restoring leg movements through intensive training on a treadmill or using robotic devices, but ignore engaging the arms. Several groups have recently shown that simultaneous arm and leg (A&L) cycling improves walking function and interlimb connectivity. These findings highlight the importance of neuronal pathways between the arm (cervical) and leg (lumbar) control regions in the spinal cord during locomotion, and emphasize the need for activating these pathways to improve walking after neural injury or disease. While the findings to date provide important evidence about actively including the arms in walking rehabilitation, these strategies have yet to be optimized. Moreover, improvements beyond A&L cycling alone may be possible with conjunctive targeted strategies to enhance spinal interlimb connectivity. The aim of this review is to highlight the current evidence for improvements in walking function and neural interlimb connectivity after neural injury or disease with cycling-based rehabilitation paradigms. Furthermore, strategies to enhance the outcomes of A&L cycling as a rehabilitation strategy are explored. These include the use of functional electrical stimulation-assisted cycling in acute care settings, utilizing non-invasive transcutaneous spinal cord stimulation to activate previously inaccessible circuitry in the spinal cord, and the use of paired arm and leg rehabilitation robotics. This review aims to consolidate the effects of exercise interventions that incorporate the arms on improved outcomes for walking, functional mobility, and neurological integrity, underscoring the importance of integrating the arms into the rehabilitation of walking after neurological conditions affecting sensorimotor function.
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(This article belongs to the Special Issue Neuromodulation: From Theories to Therapies)
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Retinal Thickness in Patients with Parkinson’s Disease and Dopa Responsive Dystonia—Is There Any Difference?
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Marko Svetel, Gorica Marić, Marija Božić, Una Lazić, Andona Milovanović, Jana Jakšić, Igor Petrović, Ana Dimitrijević, Milica Knežević and Tatjana Pekmezović
Biomedicines 2025, 13(5), 1227; https://doi.org/10.3390/biomedicines13051227 - 19 May 2025
Abstract
Background/Objectives: Certain aspects of retinal thickness assessed by optical coherence tomography (OCT) in patients with Parkinson’s disease (PD) require additional clarification. It is supposed that attributing reduced retinal thickness in PD to dopaminergic loss may not be acceptable as it also happens
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Background/Objectives: Certain aspects of retinal thickness assessed by optical coherence tomography (OCT) in patients with Parkinson’s disease (PD) require additional clarification. It is supposed that attributing reduced retinal thickness in PD to dopaminergic loss may not be acceptable as it also happens in diseases where dopaminergic loss does not occur. The objective of our study is to compare the ganglion cell/inner plexiform layer (GCIPL), peripapillary retinal nerve fiber layer (pRNFL), and macular thickness of PD and dopa responsive dystonia (DRD) patients with healthy controls (HC), to investigate whether DRD patients, as a distinctive model of genetically induced dopamine deficiency, have reduced retinal thickness in comparison with PD, and to analyze correlation between retinal thickness and various PD clinical parameters. Methods: We analyzed 86 patients with PD, 10 patients with DRD, and 96 age- and sex-matched HC. Results: GCIPL, pRNFL, and central macula thickness (CMT) are statistically significantly thinner in PD patients compared to HC (p < 0.001, all). GCIPL and CMT are also statistically significantly thinner in DRD patients compared to HC (p = 0.012, p = 0.001, respectively). GCIPL thickness correlates positively with the daily dose of levodopa (r = 0.244, p < 0.01). The thickness of GCIPL and pRNFL correlate negatively with current age (r = −0.219; p < 0.01 and r = −0.358; p < 0.05, respectively). All retinal parameters are statistically significantly thinner in females than in males (p < 0.05). Conclusions: Patients with PD and DRD did not differ in GCIPL and pRNFL thickness when compared to one another. These results, supported by positive correlation of levodopa dose and GCIPL thickness in PD patients, emphasize the importance of dopamine in maintaining retinal thickness.
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(This article belongs to the Section Neurobiology and Clinical Neuroscience)
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Ultrasound Predictors for Persistence or a Change in the Diagnosis of Rheumatoid Arthritis After 5 Years—A Prospective Cohort Study of Patients with Early Rheumatoid Arthritis
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Tanya Sapundzhieva, Lyubomir Sapundzhiev, Martin Mitev, Rositsa Karalilova and Anastas Batalov
Biomedicines 2025, 13(5), 1226; https://doi.org/10.3390/biomedicines13051226 - 19 May 2025
Abstract
Aim: To identify ultrasound (US) predictors of persistence or change in the diagnosis of rheumatoid arthritis (RA) after five years in a cohort of patients with early RA. Patients and Methods: One hundred and twenty patients with early arthritis who met the 2010
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Aim: To identify ultrasound (US) predictors of persistence or change in the diagnosis of rheumatoid arthritis (RA) after five years in a cohort of patients with early RA. Patients and Methods: One hundred and twenty patients with early arthritis who met the 2010 ACR/EULAR classification criteria for RA were followed for a period of five years. The US assessment at baseline included a bilateral evaluation of the wrists, second to fifth metacarpophalangeal (MCP) joints, second to fifth proximal interphalangeal (PIP) joints, the IV and VI extensor compartments of the wrists, and the flexor tendons of the second to fifth fingers. This evaluation was conducted using both grayscale ultrasound (GSUS) and power Doppler ultrasound (PDUS). The following scores were recorded for each patient: synovitis score, mini-enthesitis score (including paratenonitis of the finger extensor tendon at the MCP joint, central slip enthesitis at the PIP joint, pseudotenosynovitis, and the A1 pulley of the second finger), finger flexor tenosynovitis score, and tenosynovitis score for the IV and VI wrist extensor compartments. The receiver operating characteristic (ROC) curve was utilized to identify the ultrasound predictors for either maintaining or revising an initial diagnosis of RA. Results: At month 6, 82 (68%) patients were classified as having RA according to 1987 ACR RA criteria, 23 (19.2%) were diagnosed with psoriatic arthritis (PsA), 10 (8.3%) with systemic connective tissue disease (SCTD)–8 (6.7%) patients with Sjogren Syndrome and 2 (1.7%) patients with systemic lupus erythematosus (SLE)–and 5 (4.2%) patients with calcium pyrophosphate deposition disease (CPPD). The most significant predictor of RA in the fifth year was the VI extensor compartment tenosynovitis score, with an AUC of 0.915 and a criterion value > 0, associated with a sensitivity of 82.93% and a specificity of 100% (p < 0.001). The PDUS synovitis score demonstrated the second-best prognostic ability with an AUC of 0.823, a criterion value > 2, a sensitivity of 82.93%, and a specificity of 73.68% (p < 0.001). The mini-enthesitis score showed the best prognostic ability of a PsA diagnosis with an AUC of 0.998, a criterion value > 1, a sensitivity of 95.65%, and a specificity of 100% (p < 0.001). The paratenonitis score, pseudotenosynovitis score, and thickened A1 pulley were also predictive of PsA diagnosis with AUCs of 0.977, 0.955, and 0.919, respectively (p < 0.001 for all). Conclusions: Nearly one-third of the patients who were initially classified as having RA had their diagnosis revised at the end of the fifth year. Ultrasound of joints, tendons, and mini-entheses at baseline may serve as potential imaging predictive biomarkers for persistence or change in diagnosis after 5 years.
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(This article belongs to the Section Molecular and Translational Medicine)
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Inhibition of TPI1 Sensitizes Cisplatin-Resistant Oral Cancer to Ferroptosis
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Dandan Wang, Huimin Zheng, Yumin Chen, Jialin Hao, Yuan Zhou and Nan Li
Biomedicines 2025, 13(5), 1225; https://doi.org/10.3390/biomedicines13051225 - 19 May 2025
Abstract
Background: Iron metabolism has emerged as a critical factor in cancer biology, with elevated intracellular iron levels contributing to increased oxidative stress and tumorigenesis. However, the molecular determinants governing ferroptosis sensitivity remain incompletely understood. Triosephosphate isomerase 1 (TPI1), a key glycolytic enzyme, has
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Background: Iron metabolism has emerged as a critical factor in cancer biology, with elevated intracellular iron levels contributing to increased oxidative stress and tumorigenesis. However, the molecular determinants governing ferroptosis sensitivity remain incompletely understood. Triosephosphate isomerase 1 (TPI1), a key glycolytic enzyme, has been implicated in cancer progression, but its role in ferroptosis regulation, particularly in the context of chemoresistance, is largely unexplored. In this study, we investigated the impact of TPI1 silencing on ferroptosis in cisplatin-resistant oral squamous cell carcinoma (OSCC), aiming to elucidate its mechanistic role and therapeutic potential. Methods: We conducted in vitro and in vivo analyses to evaluate the functional consequences of TPI1 knockdown in cisplatin-resistant OSCC cell lines and tumor xenograft models. The effects of TPI1 silencing and/or cisplatin treatment were assessed with respect to cell proliferation, migration, and invasion, along with ferroptosis-associated markers, including lipid ROS, free iron levels, lipid peroxidation, and the expression of key ferroptosis-related genes. Additionally, we analyzed the clinical relevance of TPI1 expression in human OSCC tissue samples, examining its association with clinicopathological features and patient prognosis. Results: TPI1 was found to be significantly upregulated in both OSCC tissues and cell lines, and high TPI1 expression correlated with poor clinical outcomes. Multivariate analysis identified TPI1 as an independent prognostic factor for tumor progression. Functionally, TPI1 knockdown suppressed OSCC cell proliferation, migration, and invasion, while its overexpression enhanced these oncogenic behaviors. Mechanistically, silencing TPI1 led to increased intracellular ROS accumulation, elevated free iron, and enhanced lipid peroxidation, collectively promoting ferroptotic cell death in cisplatin-resistant OSCC cells. In vivo, TPI1 depletion resulted in marked tumor growth inhibition and synergized with cisplatin to further suppress tumor burden in xenograft models. Moreover, TPI1 silencing disrupted the epithelial–mesenchymal transition (EMT), a key driver of cancer metastasis and drug resistance. Conclusions: Our study reveals a previously unrecognized role of TPI1 in protecting oral cancer cells from ferroptosis, especially in the setting of cisplatin resistance. These findings suggest that TPI1 not only contributes to tumor aggressiveness but also mediates resistance to ferroptosis. Targeting TPI1 may therefore represent a promising therapeutic strategy to overcome chemoresistance and enhance ferroptosis-based therapies in oral cancer.
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(This article belongs to the Section Cancer Biology and Oncology)
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The Development and Assessment of a Unique Disulfidptosis-Associated lncRNA Profile for Immune Microenvironment Prediction and Personalized Therapy in Gastric Adenocarcinoma
by
Jiyue Zhu, Xiang Zhu, Tingting Su, Huiqing Zhou, Shouhua Wang and Weibin Shi
Biomedicines 2025, 13(5), 1224; https://doi.org/10.3390/biomedicines13051224 - 19 May 2025
Abstract
Background: Long non-coding RNAs (lncRNAs) are crucial factors affecting the occurrence, progression, and prognosis of gastric carcinoma (GC). The accumulation of disulfide bonds to excessive levels in cells expressing high SLC7A11 triggers disulfidptosis, which functions as a regulated form of cellular death. Research
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Background: Long non-coding RNAs (lncRNAs) are crucial factors affecting the occurrence, progression, and prognosis of gastric carcinoma (GC). The accumulation of disulfide bonds to excessive levels in cells expressing high SLC7A11 triggers disulfidptosis, which functions as a regulated form of cellular death. Research has demonstrated that upregulated SLC7A11 is common in human cancers, but the effect of disulfidptosis on GC remains unclear. Identifying lncRNAs associated with disulfidptosis (drlncRNAs) and establishing a prognostic risk profile holds considerable importance for advancing GC research and treatment. Methods: Clinical records and transcriptomic datasets from individuals with GC were acquired from The Cancer Genome Atlas (TCGA) repository. A three-drlncRNA risk model was built using three common regression analysis methods. Then we used receiver operating characteristic (ROC) curves, independent prognostic analysis, and additional statistical approaches to assess the precision of the model. This investigation additionally encompassed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, immune cell infiltration evaluation, and pharmacological sensitivity predictions. To further investigate immunotherapy response disparities between patient cohorts with elevated- and reduced-risk scores, analyses of tumor mutational burden (TMB), tumor immune dysfunction and exclusion (TIDE), and microsatellite instability (MSI) were implemented. Results: We constructed a unique model composed of three drlncRNAs (AC107021.2, AC016394.2, and AC129507.1). Its independent prognostic capability for GC patients was validated through both single-variable and multivariable Cox regression analyses. GO and KEGG pathway assessments revealed predominant enrichment within the elevated-risk cohort, particularly in pathways involving sulfur compound interactions, traditional Wnt signaling mechanisms, cell-substrate adherens junctions, and cAMP signaling cascades, among others. Tumor microenvironment (TME) evaluation demonstrated elevated ImmuneScores, StromalScores, and ESTIMATEScores within the high-risk patient population. Concurrently, this elevated-risk cohort exhibited enhanced immune cell infiltration patterns, whereas the reduced-risk group displayed superior expression of immune checkpoints (ICPs). Additional investigations revealed that patients categorized into the reduced-risk classification possessed greater tumor mutational burden, increased MSI-high proportions, and diminished tumor immune dysfunction and exclusion scores compared to their high-risk counterparts. Pharmacological sensitivity assessments confirmed the superior efficacy of several therapeutic agents, including gemcitabine and veliparib (ABT.888), in patients with lower risk classifications. Conclusions: Our established risk stratification system demonstrates independent prognostic predictive capacity while offering personalized clinical intervention guidance for individuals diagnosed with GC.
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(This article belongs to the Section Molecular and Translational Medicine)
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Extended Toxicity, Genotoxicity, and Mutagenicity of Combination of pBudK-coVEGF-coANG and pBudK-coGDNF Plasmids in Preclinical Trials
by
Igor V. Samatoshenkov, Alexander M. Aimaletdinov, Elena Y. Zakirova, Egan L. Kalmykov, Rustam Khodzhibaev, Yulia M. Samatoshenkova, Ilnur M. Ganiev, Marat S. Kadyrov and Yana O. Mukhamedshina
Biomedicines 2025, 13(5), 1223; https://doi.org/10.3390/biomedicines13051223 - 18 May 2025
Abstract
Chronic lower limb ischemia is a debilitating condition, particularly prevalent among elderly patients and individuals ineligible for revascularization procedures. Gene therapy aimed at promoting therapeutic angiogenesis presents a promising alternative treatment strategy. Objectives: This study evaluated the preclinical safety of a gene therapy
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Chronic lower limb ischemia is a debilitating condition, particularly prevalent among elderly patients and individuals ineligible for revascularization procedures. Gene therapy aimed at promoting therapeutic angiogenesis presents a promising alternative treatment strategy. Objectives: This study evaluated the preclinical safety of a gene therapy drug composed of the plasmids pBudK-coVEGF-coANG and pBudK-coGDNF in laboratory animals. Safety assessment followed a single intramuscular injection at a dose 30 times higher than the proposed therapeutic level. Methods: Acute toxicity was monitored over a 24-h period. Genotoxicity was assessed using the micronucleus test at doses of 200, 1000, and 5000 μg/kg. Bone marrow cytology was analyzed to detect hematopoietic toxicity. Delayed toxicity was evaluated over a two-week recovery period. Results: No signs of acute toxicity were observed, even at the highest dose. The micronucleus test revealed no genotoxic effects, with no significant increase in micronucleated polychromatic erythrocytes compared to control groups. Bone marrow erythroblast parameters remained within normal physiological ranges. Additionally, no delayed adverse effects were detected during the recovery period. Conclusions: The gene therapy drug demonstrated a favorable preclinical safety profile, exhibiting no evidence of toxicity or genotoxicity, even at substantially elevated doses. These findings support the continued development of this therapy as a potential treatment for chronic lower limb ischemia in patients who are not candidates for surgical intervention.
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(This article belongs to the Section Gene and Cell Therapy)
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Genetic Analysis of CYP1B1 and Other Anterior Segment Dysgenesis-Associated Genes in Latvian Cohort of Primary Congenital Glaucoma
by
Eva Elksne, Baiba Lace, Janis Stavusis, Anastasija Tvoronovica, Pawel Zayakin, Eriks Elksnis, Arturs Ozolins, Ieva Micule, Sandra Valeina and Inna Inashkina
Biomedicines 2025, 13(5), 1222; https://doi.org/10.3390/biomedicines13051222 - 18 May 2025
Abstract
Background: Primary congenital glaucoma (PCG) is a rare disease with an incidence of 1 in 12,000 to 18,000 in Europeans. The scarcity of the disease and limited access to genetic testing have hindered research, particularly within the Latvian population. Objectives: This
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Background: Primary congenital glaucoma (PCG) is a rare disease with an incidence of 1 in 12,000 to 18,000 in Europeans. The scarcity of the disease and limited access to genetic testing have hindered research, particularly within the Latvian population. Objectives: This study aims to present the preliminary results of a molecular genetic investigation into PCG in a Latvian cohort and to compare the prevalence of gene CYP1B1 variants with other European studies as well as to the general population in Latvia. Methods: Twenty probands with clinically diagnosed PCG and 36 family members enrolled in the study. Genetic testing was conducted using genomic DNA from peripheral blood using next generation sequencing (NGS) of seven selected genes: CYP1B1, FOXC1, FOXE3, PXDN, PITX2, PITX3, PAX6, and CPAMD8. Four probands had whole-genome sequencing (WGS). Results: All participants were of European ancestry, with no family history of PCG. Most probands were diagnosed in their first year of life, with a female to male ratio of 1:1.2 and with 80.0% of cases being unilateral. No CYP1B1 pathogenic variants were identified in the screened subjects. However, a heterozygous missense variant c.4357C>A (p.Pro4357Thr) in the PXDN gene was found in one proband and one of her parents that was classified as a variant of uncertain significance. Conclusions: This study represents the first genetic characterization of PCG in the Latvian population. Using NGS, we identified no pathogenic variants in the CYP1B1 gene among affected individuals. Preliminary evidence from this cohort does not support CYP1B1 variants as a predominant cause of PCG, though larger studies are needed to confirm this observation. Comprehensive genetic screening using whole-exome or whole-genome sequencing will be essential to identify the underlying genetic etiology of PCG in Latvia.
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(This article belongs to the Special Issue Ophthalmic Genetics: Unraveling the Genomics of Eye Disorders)
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Advances in the Treatment of Acute Myeloid Leukemia: Implications for Low- and Middle-Income Countries
by
Michelle Morcos-Sandino, Sofia Isabel Quezada-Ramírez and Andrés Gómez-De León
Biomedicines 2025, 13(5), 1221; https://doi.org/10.3390/biomedicines13051221 - 18 May 2025
Abstract
Acute myeloid leukemia (AML) presents a significant global health challenge due to its aggressive behavior and mortality rates. Traditionally, AML treatment has relied on intensive chemotherapy—anthracyclines and cytarabine. However, recent breakthroughs in targeted therapies are transforming clinical practices. This review examines current treatment
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Acute myeloid leukemia (AML) presents a significant global health challenge due to its aggressive behavior and mortality rates. Traditionally, AML treatment has relied on intensive chemotherapy—anthracyclines and cytarabine. However, recent breakthroughs in targeted therapies are transforming clinical practices. This review examines current treatment strategies, including breakthrough therapies. Also, a global perspective on AML management includes the disparity in treatment availability, particularly the difficulties faced by low- and middle-income countries due to the high cost and restricted access to novel therapies.
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(This article belongs to the Special Issue Advances in the Pathogenesis and Treatment of Acute Myeloid Leukemia)
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Palm Tocotrienol Preserves Trabecular Osteocyte Indices and Modulates the Expression of Osteocyte Markers in Ovariectomized Rats
by
Sophia Ogechi Ekeuku, Shafiq Zikry Zarir, Anis Nazira Razali, Syamima Mohamad Zaidi, Noor Halinah Mohamed Ali Jinnah, Muhamed Lahtif Nor Muhamad, Sok Kuan Wong and Kok-Yong Chin
Biomedicines 2025, 13(5), 1220; https://doi.org/10.3390/biomedicines13051220 - 18 May 2025
Abstract
Background/Objective: Palm tocotrienol has bone-protective properties in animal models, yet its underlying mechanism remains unclear. Given osteocytes’ role in bone homeostasis, this research aimed to investigate the effects of palm tocotrienol on the quantity of osteocytes and the expression of osteocyte-specific markers in
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Background/Objective: Palm tocotrienol has bone-protective properties in animal models, yet its underlying mechanism remains unclear. Given osteocytes’ role in bone homeostasis, this research aimed to investigate the effects of palm tocotrienol on the quantity of osteocytes and the expression of osteocyte-specific markers in ovariectomized rats. Methods: Adult female rats (Sprague Dawley; three-month-old; n = 6/group) were randomly divided into baseline, sham control, ovariectomized control, unemulsified palm tocotrienol (UPT), emulsified palm tocotrienol (EPT), and positive control. The baseline group was euthanized without intervention, whereas the sham group underwent a laparotomy procedure in which the ovaries were not excised. The other groups underwent bilateral removal of the ovaries and subsequently received UPT (100 mg/kg/day, 50% vitamin E), EPT (100 mg/kg/day, 25% vitamin E), or a combination of glucosamine sulfate (250 mg/kg/day) and calcium carbonate (1% in drinking water). Control groups were induced with similar gavage stress with olive oil. After 10 weeks, all rats were sacrificed for bone and serum analysis. Results: UPT and EPT significantly increased trabecular osteocyte and total lacunae numbers (p < 0.05 versus ovariectomized control). Both treatments significantly reduced mRNA expression levels of dentin matrix protein-1 (p < 0.05 versus ovariectomized control), whereas sclerostin mRNA expression was unchanged (p > 0.05 versus ovariectomized control). However, neither UPT nor EPT improved circulating or skeletal redox status (p > 0.05 versus ovariectomized control). Conclusions: Palm tocotrienol may support bone health by preserving the quantity of trabecular osteocytes and modulating osteocyte-mediated bone remodeling. Further research is required to elucidate its precise mechanisms.
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(This article belongs to the Special Issue Pathogenesis and Novel Therapeutics in Musculoskeletal Conditions, 3rd Edition)
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Human Placenta Hydrolysate Protects Against Acetaminophen-Induced Liver Injury in Mice
by
Inyoung Hwang, Chi-Gu Kang, So-Jung Lim, Hyun-Jin Kim, Ryun Kang, So-Hyun Jeon, Sang-Hoon Lee, Jae-Won Kim and Ju-Seop Kang
Biomedicines 2025, 13(5), 1219; https://doi.org/10.3390/biomedicines13051219 - 18 May 2025
Abstract
Background/Objectives: Acetaminophen (APAP) is a widely used analgesic and antipyretic, but overdose can lead to APAP-induced liver injury (AILI), a major cause of acute liver failure. While N-acetylcysteine (NAC) is the current standard of care, its efficacy is significantly reduced when administered
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Background/Objectives: Acetaminophen (APAP) is a widely used analgesic and antipyretic, but overdose can lead to APAP-induced liver injury (AILI), a major cause of acute liver failure. While N-acetylcysteine (NAC) is the current standard of care, its efficacy is significantly reduced when administered after the peak time of liver injury, highlighting the need for alternative therapeutic strategies. Human placenta hydrolysate (HPH) has shown potential as a therapeutic agent for various liver diseases due to its rich content of bioactive compounds. This study aimed to investigate the hepatoprotective effects of HPH in a mouse model of AILI. Methods: HPH was administered to mice for three days prior to APAP treatment. The effects of HPH on liver morphology, necrosis, liver enzymes, phase I/II detoxification enzymes, oxidative stress markers, and inflammatory cytokines were evaluated. Results: HPH pretreatment attenuated APAP-induced liver necrosis and congestion, reduced serum levels of liver enzymes. In addition, HPH showed a concentration-dependent attenuation of APAP-induced decrease in human hepatocyte viability. HPH modulated phase I/II enzyme expression by downregulating CYP2E1 and upregulating SULT1A1, UGT1A6, GSTP1, and TPMT. HPH also exhibited antioxidant effects by increasing SOD and GPx activities, reducing MDA levels, and restoring the GSH/GSSG ratio. Furthermore, HPH attenuated the APAP-induced increase in the inflammatory cytokines TNF-α and IL-6. These findings suggest that HPH protects against AILI through multiple mechanisms, including the modulation of phase I/II detoxification, activation of antioxidants, and inhibition of inflammation. Conclusions: HPH could be a potential therapeutic option for APAP overdose and related liver injuries.
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(This article belongs to the Special Issue Hepatotoxicity: From Pathology to Novel Therapeutic Approaches (2nd Edition))
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Human and Mouse Bone Marrow CD45+ Erythroid Cells Have a Constitutive Expression of Antibacterial Immune Response Signature Genes
by
Roman Perik-Zavodskii, Olga Perik-Zavodskaia, Julia Shevchenko, Kirill Nazarov, Anastasia Gizbrekht, Saleh Alrhmoun, Vera Denisova and Sergey Sennikov
Biomedicines 2025, 13(5), 1218; https://doi.org/10.3390/biomedicines13051218 - 17 May 2025
Abstract
Introduction: Recent studies have shown that Erythroid progenitor cells exhibit a distinct immunosuppressive and immunoregulatory phenotype associated with the response to bacteria. Methods: The objective of this study was to comprehensively explore the traits of human bone marrow Erythroid cells through
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Introduction: Recent studies have shown that Erythroid progenitor cells exhibit a distinct immunosuppressive and immunoregulatory phenotype associated with the response to bacteria. Methods: The objective of this study was to comprehensively explore the traits of human bone marrow Erythroid cells through protein–protein interaction network analysis using cytokine secretion analysis, and single-cell immunoproteomic analysis using flow cytometry, as well as the re-analysis of publicly available human and mouse bone marrow Erythroid-cell transcriptomic data. Results: Our protein–protein interaction network analysis of human bone marrow Erythroid-cell protein-coding genes identified enrichment in the immune response to lipopolysaccharide, with Calprotectin and Cathepsin G being the main factors. We then mapped the Calprotectin to the CD45+ Erythroid cells of both humans and mice via the analysis of the publicly available scRNA-seq data. Additionally, we observed that human bone marrow Erythroid cells secrete cytokines and chemokines, such as IL-1b, IL-8, and IL-18, which are also mainly involved in the immune response to lipopolysaccharide. We also found that human and mouse bone marrow Erythroid-cell conditional media inhibit bacterial growth in vitro. Discussion: These findings suggest that both human and mouse bone marrow CD45+ Erythroid cells possess the potential to combat pathogenic microbes and thus play a role in innate antimicrobial immunity. Conclusions: CD45+ Erythroid cells are a potent immunoregulatory cell population in both humans and mice.
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(This article belongs to the Section Immunology and Immunotherapy)

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