Biomedicines

20 pages, 2063 KB

Open AccessArticle

The Association of Elevated Factor VIII and von Willebrand Factor (vWF) Levels with SYNTAX Score in Patients with Chronic Coronary Syndrome

by Predrag Djuric, Zorica Mladenovic, Zoran Jovic, Snjezana Vukotic, Marijan Spasic, Mirjana Mijuskovic, Brankica Terzic, Zoran Radojicic, Nina Radisavljevic, Marko Djuric and Dragan Djuric

Biomedicines 2025, 13(9), 2284; https://doi.org/10.3390/biomedicines13092284 (registering DOI) - 17 Sep 2025

Abstract

Background and Objectives: Factor VIII (FVIII) and the von Willebrand factor (vWF) are key components of hemostatic balance. Disruption of the vWF-ADAMTS13 axis, characterized by elevated vWF and reduced ADAMTS13 activity has been implicated in thrombotic disorders, including COVID-19-asscoiated coagulopathy, where this imbalance [...] Read more.

Background and Objectives: Factor VIII (FVIII) and the von Willebrand factor (vWF) are key components of hemostatic balance. Disruption of the vWF-ADAMTS13 axis, characterized by elevated vWF and reduced ADAMTS13 activity has been implicated in thrombotic disorders, including COVID-19-asscoiated coagulopathy, where this imbalance correlates with disease severity and mortality. This study evaluated the relationship between plasma FVIII and vWF levels and the severity of coronary artery disease (CAD), as assessed by the SYNTAX score. Methods: We enrolled 82 patients with chronic coronary syndrome (CCS) and a positive treadmill test who underwent elective coronary angiography. Based on the SYNTAX score, patients were divided into three groups: Group I (≤22), Group II (23–32), and Group III (≥33). Results: FVIII levels varied significantly (Group I: 2.25 ± 0.75; Group III: 2.97 ± 0.95; p = 0.007), with an OR of 3.632 (95% CI: 1.116–11.826; p = 0.03). vWF levels differed significantly across SYNTAX groups (Group I: 1.16 ± 0.59; Group II: 1.52 ± 0.62; Group III: 1.49 ± 0.80; p = 0.040). vWF > 1.75 was more frequent in Groups II and III, with an odds ratio (OR) of 4.909 (95% CI: 1.429–16.864; p = 0.01) for Group III vs. Group I. Fibrinogen and C-reactive protein (CRP) were elevated in patients with SYNTAX scores ≥33. In multinomial logistic regression analysis, FVIII emerged as the sole independent predictor of CAD complexity (p = 0.004), while the vWF showed significance in pairwise comparison (Group II vs. Group I; OR = 3.433, p = 0.049). Conclusions: This study demonstrated significant differences in hemostatic and inflammatory biomarkers across SYNTAX score categories reflecting CAD severity in CCS patients. FVIII emerged as an independent predictor of CAD complexity, while the vWF demonstrated significant associations in specific subgroup comparisons. The observed vWF-ADAMTS13 axis dysregulation supports the rationale for investigating vWF-targeted therapeutics, including agents such as caplacizumab, in cardiovascular disease management. These findings require validation in larger studies. Full article

(This article belongs to the Special Issue Cardiovascular and Metabolic Disease: New Treatment and Future Directions—4th Edition)

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5 pages, 187 KB

Open AccessEditorial

Recent Advances in Parkinson’s Disease Research: From Pathophysiology to Novel Therapeutic Approaches

by Sujung Yeo

Biomedicines 2025, 13(9), 2283; https://doi.org/10.3390/biomedicines13092283 (registering DOI) - 17 Sep 2025

Abstract

Parkinson’s disease is a progressive neurodegenerative disorder affecting approximately 1–2% of the population over 65 years of age [...] Full article

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

22 pages, 378 KB

Open AccessReview

Reimagining Oncologic Drugs in Atherosclerosis: Emerging Mechanisms and Therapeutic Potential

by George Liu, Guillaume De Vlaminck, Osayamen Atekha, Eric P. Grewal, Rishab Ramapriyan and Gautam Agarwal

Biomedicines 2025, 13(9), 2282; https://doi.org/10.3390/biomedicines13092282 (registering DOI) - 17 Sep 2025

Abstract

Atherosclerosis is a chronic vascular disease that underlies the pathogenesis of both peripheral arterial disease and coronary artery disease, two of the leading causes of morbidity and mortality worldwide. Characterized by the accumulation of lipids, chronic inflammation, and fibrotic remodeling within vasculature, atherosclerosis [...] Read more.

Atherosclerosis is a chronic vascular disease that underlies the pathogenesis of both peripheral arterial disease and coronary artery disease, two of the leading causes of morbidity and mortality worldwide. Characterized by the accumulation of lipids, chronic inflammation, and fibrotic remodeling within vasculature, atherosclerosis involves a complex interplay of endothelial dysfunction, immune dysregulation, vascular smooth muscle cell proliferation, and maladaptive neovascularization. Increasing evidence now suggests that atherosclerosis has notable overlap with cancer biology, including sustained proliferative signaling, evasion of immune surveillance, angiogenesis, and resistance to cell death. These shared molecular features have prompted growing interest in the potential repurposing of oncologic treatments in the modulation of atherosclerotic disease. While preclinical data are promising, successful translation and integration of oncologic therapeutics will require overcoming critical barriers, including drug toxicity, long-term safety, regulatory constraints, and cost-effectiveness. Future work should focus on biomarker-guided patient selection, dose optimization, and targeted delivery systems to minimize off-target effects while enhancing efficacy. Full article

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

8 pages, 493 KB

Open AccessBrief Report

The Incidence of IgG4-Related Disease in Slovenia—Single-Centre Experience

by Alojzija Hočevar, Aleš Grošelj, Gregor Hawlina, Matic Koželj, Andrej Škoberne, Jože Pižem and Vesna Jurčić

Biomedicines 2025, 13(9), 2281; https://doi.org/10.3390/biomedicines13092281 (registering DOI) - 17 Sep 2025

Abstract

Background: Data on the incidence of IgG4-related disease (IgG4-RD) are scarce. Our aim was to determine the incidence of IgG4-RD in a well-defined region. Methods: This retrospective study covered the Ljubljana region over the period from January 2012 to December 2024. A review [...] Read more.

Background: Data on the incidence of IgG4-related disease (IgG4-RD) are scarce. Our aim was to determine the incidence of IgG4-RD in a well-defined region. Methods: This retrospective study covered the Ljubljana region over the period from January 2012 to December 2024. A review of cases diagnosed with IgG4-RD was performed at several departments of the University Medical Centre Ljubljana—an integrated secondary/tertiary university teaching hospital (rheumatology, nephrology, angiology, gastroenterology, abdominal surgery, ENT surgery, ophthalmology). While IgG4-RD cases at the Department of Rheumatology were collected prospectively, potential cases at other departments were retrieved by searching electronic medical database for the keyword “IgG4”. In addition, the Institute of Pathology, Faculty of Medicine, University of Ljubljana, provided a list of patients with histological features consistent with IgG4-RD. Year-specific incidence rates and an average incidence rate over the 13-year period were determined. Clinical features of patients were analysed. Results: During the observation period, 58 cases of IgG4-RD were diagnosed. Of these, 35 patients were residents of the Ljubljana region, which had an average adult population of 541,600. The estimated average annual incidence rate of IgG4-RD was 5.0 per million (95% confidence interval: 3.5; 6.9), with year-specific incidence rates fluctuating between 1.8 and 9.3 per million adults. The cases were stratified into four phenotypic categories: pancreato-hepato-biliary (17%), retroperitoneal fibrosis-aortitis (43%), head and neck-limited (14%), and Mikulicz syndrome with systemic involvement (26%). Conclusions: The average annual incidence rate of IgG4-RD was 5 per million adults, with the retroperitoneal fibrosis-aortitis phenotype predominating in our cohort. Full article

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

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16 pages, 3124 KB

Open AccessArticle

The Prevalence of Diamine Oxidase Polymorphisms and Their Association with Histamine Intolerance Symptomatology in the Mexican Population

by Pamela Aguilar-Rodea, Viviana Mejía-Ramírez, Raúl Hernández-Munguía, Saúl Ramírez-Vargas, Diana Tovar-Vivar, Jaquelin Leyva-Hernández, Juan Carlos Nacar-Gutiérrez, Miriam Morales-Martínez and Aracely Palafox-Zaldivar

Biomedicines 2025, 13(9), 2280; https://doi.org/10.3390/biomedicines13092280 (registering DOI) - 17 Sep 2025

Abstract

Exogenous histamine obtained from the intake of histamine-rich food is mainly metabolized by the diamine oxidase enzyme (DAO). Histamine intolerance (HIT) is an alteration mainly caused by DAO deficiency, which is commonly associated with gastrointestinal, respiratory, cardiovascular, central nervous system, muscular, skeletal, and [...] Read more.

Exogenous histamine obtained from the intake of histamine-rich food is mainly metabolized by the diamine oxidase enzyme (DAO). Histamine intolerance (HIT) is an alteration mainly caused by DAO deficiency, which is commonly associated with gastrointestinal, respiratory, cardiovascular, central nervous system, muscular, skeletal, and skin symptoms. Despite four single-nucleotide polymorphisms (SNPs) being mainly associated with DAO deficiency, the probability of inheriting these variants and their relationship with HIT in the Mexican population remain unknown. Objective: The aim of this study was to evaluate the prevalence of these SNPs and their relationships with HIT in the Mexican population, including both individual volunteers and family groups. Methods: Four SNPs related to DAO deficiency were detected in 112 volunteers; medical questionnaires were answered. Results: The prevalence of genetic DAO deficiency attributed to at least one risk allele was 78.57% (rs1049793 was the main SNP). Fifteen DAO SNP combinations were detected (the main rs2052129, rs10156191, rs1049742 (wild-type homozygotes), and rs1049793 (heterozygote), 31.25%). A total of 41.07% of the volunteers presented at least three symptoms in different systems related to HIT, of whom 84.78% presented at least one SNP. The DAO deficiency genetic risk score varied among individual volunteers and families. The highest probability of having a mutated homozygote was 11.8% (rs1049793). HIT symptoms varied among relatives sharing identical genotypes. Conclusions: The prevalence of SNPs related to DAO deficiency in the Mexican population correlates with globally reported data; however, further analysis with volunteers distributed throughout the country would be desirable. Although genetic predisposition was common, the presence of SNPs alone did not predict specific HIT symptoms. Multiple SNPs may increase the presence of HIT symptoms, regardless of the type of allele. These findings highlight the multifactorial nature of HIT and underscore the need for standardized diagnostic criteria. Full article

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

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15 pages, 6465 KB

Open AccessArticle

Valemetostat–SAHA-Driven Acetylation of p53 via SET/TAF-Iβ Displacement and p300 Activation Modulates Cell Cycle Regulators in Pancreatic Cancer Cells

by Michele Di Crosta, Francesca Chiara Ragone, Rossella Benedetti, Gabriella D’Orazi, Roberta Santarelli, Maria Saveria Gilardini Montani and Mara Cirone

Biomedicines 2025, 13(9), 2279; https://doi.org/10.3390/biomedicines13092279 - 17 Sep 2025

Abstract

Background/Objective: Aberrant acetylation and methylation of histone and non-histone proteins contribute to carcinogenesis. Among non-histone proteins, wild-type (wt) p53 is particularly notable for the critical role that acetylation and methylation play in regulating its stability and function. Although with opposite outcomes, these post-translational [...] Read more.

Background/Objective: Aberrant acetylation and methylation of histone and non-histone proteins contribute to carcinogenesis. Among non-histone proteins, wild-type (wt) p53 is particularly notable for the critical role that acetylation and methylation play in regulating its stability and function. Although with opposite outcomes, these post-translational modifications (PTMs) can also affect mutant forms of p53 (mutp53), which are frequently detected in cancers. These proteins may acquire oncogenic properties, activating signaling pathways that promote carcinogenesis. Acetylation activates wtp53, while this PTM has been shown to destabilize mutp53, reducing cancer aggressiveness and improving the efficacy of anticancer therapies. In this study, we investigated the possibility of targeting mutp53 in pancreatic cancer cells by using a combination of EZH2 and HDAC inhibitors. Methods: Western blotting, qRT-PCR, and ChIP experiments were performed to address this question. Results: We found that the EZH2 inhibitor Valemetostat (DS) in combination with the histone deacetylase inhibitor SAHA displaced the SET/TAF-Iβ oncoprotein from mutp53 and increased its interaction with the acetyltransferase p300, which was responsible for p53 acetylation. Moreover, mutp53 was downregulated, p21 was upregulated, and CHK1 was reduced, increasing DNA damage and leading to a stronger impairment of pancreatic cancer cell survival compared with single-agent treatments. Conclusions: Our results reveal that combining epigenetic drugs such as Valemetostat and SAHA could be exploited to target mutp53 and improve the outcome of treatments for aggressive tumors harboring it, such as in pancreatic cancer. Full article

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

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26 pages, 989 KB

Open AccessReview

Pharmaco-Epigenetics and Epigenetic Drugs in Type 2 Diabetes: Can Epigenetics Predict Drug Efficiency?

by Senzosenkosi Surprise Mkhize, Anil Amichund Chuturgoon, Terisha Ghazi and Kgothatso Eugene Machaba

Biomedicines 2025, 13(9), 2278; https://doi.org/10.3390/biomedicines13092278 - 16 Sep 2025

Abstract

Type 2 Diabetes Mellitus (T2DM) is increasingly affecting individuals across various age groups due to inadequate insulin action and secretion. It has become the leading cause of mortality worldwide, with an estimated 9.3% of the global population currently affected. Recent epigenetic studies have [...] Read more.

Type 2 Diabetes Mellitus (T2DM) is increasingly affecting individuals across various age groups due to inadequate insulin action and secretion. It has become the leading cause of mortality worldwide, with an estimated 9.3% of the global population currently affected. Recent epigenetic studies have shown that variations such as DNA methylation and histone modifications are implicated in the development of T2DM. However, epigenetically related conditions are known to be reversible, which could potentially pave the way for predicting and treating T2DM. This has led to the development of epigenetic modifier drugs, including histone deacetylase inhibitors (HDACi), histone acetyltransferase inhibitors (HATi), protein arginine methyltransferase inhibitors (PRMTi), DNA methyltransferase inhibitors (DNMTi), histone demethylating inhibitors (HDMi), and sirtuin-activating compounds (STAC). A major challenge with these epigenetic drugs is that only a few have been approved for treating metabolic diseases due to their potential to negatively impact off-target genes. The low specificity of these drugs can lead to side effects and increased toxicity, contributing to complex diseases such as cancer. Hence, gaining a comprehensive understanding of the epigenetic mechanisms underlying metabolic diseases can provide new insights and strategies for preventing, diagnosing, and treating metabolic disorders, such as T2DM. This review summarizes the epigenetic variations in T2DM, pharmaco-epigenetics, and the challenges surrounding epigenetics. This provides basic insight into the discovery of novel drug targets, which can lead to the development of epigenetic therapies for T2DM. Hence, the reversible nature of epigenetic variations retains hope for future novel strategies to combat T2DM. Full article

(This article belongs to the Special Issue Molecular Mechanisms and Translational Research on Insulin Resistance)

16 pages, 1717 KB

Open AccessArticle

Structural Proteins at Neuromuscular Junction Are Downgraded While NRG1 and Agrin Gene Expression Increases After Muscle Injury

by Jurandyr Pimentel Neto, Lara Caetano Rocha-Braga, Matheus Bertanha Fior, Paula Oliveira Camargo and Adriano Polican Ciena

Biomedicines 2025, 13(9), 2277; https://doi.org/10.3390/biomedicines13092277 - 16 Sep 2025

Abstract

Background/Objectives: The neuromuscular junction (NMJ) is the area where peripheral nerves communicate with muscle tissue. Muscle injury can occur as part of an acute degenerative process at the NMJ. This study aims to investigate the remodeling of the NMJ after a muscle injury [...] Read more.

Background/Objectives: The neuromuscular junction (NMJ) is the area where peripheral nerves communicate with muscle tissue. Muscle injury can occur as part of an acute degenerative process at the NMJ. This study aims to investigate the remodeling of the NMJ after a muscle injury in an experimental model. Methods: We used sixty male Wistar rats divided into five groups: a control group (C) and four muscle injury groups (MI) at different time points: 0 h, 24 h, 48 h, and 7 d after injury. We subjected the right hind limb to muscle injury and dissected the gastrocnemius muscles for analysis. We employed light microscopy to examine cell nuclei and the connective tissue, immunostaining to identify and measure the pre- and postsynaptic regions as well as calcium channels (P/Q), and real-time PCR to assess the gene expression of NRG1 and Agrin. Results: Our findings revealed an accumulation of nuclei and connective tissue in the acute injury groups (0 to 48 h). The morpho-quantitative analyses showed that the presynaptic structures and calcium channels underwent similar remodeling due to their morpho-functional relationship. Meanwhile, the postsynaptic receptors were significantly affected by the degenerative and inflammatory processes. These results can be linked to increased expression of NRG1 and Agrin in the acute injury groups. Conclusions: In conclusion, the synaptic regions displayed substantial adaptations within the first 48 h, with the presynaptic region recovering rapidly and the postsynaptic region recovering slowly. This relationship suggests that significant increases in Agrin and NRG1 play a crucial role in maintaining the integrity of these structures. Full article

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

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13 pages, 994 KB

Open AccessReview

Recent Progress in Keloid Mechanism and Treatment: A Comprehensive Review

by Lucia Merlino, Mattia Dominoni, Martina Rita Pano, Marianna Francesca Pasquali, Roberto Senatori, Grazia Zino and Barbara Gardella

Biomedicines 2025, 13(9), 2276; https://doi.org/10.3390/biomedicines13092276 - 16 Sep 2025

Abstract

Keloids are abnormal fibroproliferative responses in the skin that often occur without an apparent injury. Their pathogenesis remains incompletely understood, though genetic, environmental, and biochemical factors are believed to contribute. Topical medications (mostly TCA injection) are the most used treatments followed by surgery, [...] Read more.

Keloids are abnormal fibroproliferative responses in the skin that often occur without an apparent injury. Their pathogenesis remains incompletely understood, though genetic, environmental, and biochemical factors are believed to contribute. Topical medications (mostly TCA injection) are the most used treatments followed by surgery, alone or in association with other therapeutic options. In most cases, improvement has been described. A combination of altered collagen synthesis, overactive fibroblasts, and immune response contributes to keloid formation. Genomic studies have identified specific mutations, and the role of growth factors such as TGF-β has been confirmed as a key player in keloid pathogenesis. Although great improvements have been made from the molecular point of view and keloids are more easily diagnosed and treatable nowadays, they remain very challenging, having a great impact on quality of life. Their recurrence is still very high. Understanding genetic predisposition and microenvironmental influences is critical for developing more effective therapies. Advances in molecular research and clinical strategies are improving our understanding of keloids, but further studies are needed to establish precise diagnostic markers and more effective long-term treatments. Full article

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

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13 pages, 2101 KB

Open AccessArticle

High PEEP Increases Airway Dead Space and Decreases Alveolar Ventilation: A New Technique for Volumetric Capnography

by Masashi Zuiki, Kazunori Watanabe, Norihiro Iwata, Rika Mitsuno, Madoka Konishi, Akio Yamano, Eisuke Ichise, Hidechika Morimoto, Kanae Hashiguchi, Tatsuji Hasegawa and Tomoko Iehara

Biomedicines 2025, 13(9), 2275; https://doi.org/10.3390/biomedicines13092275 - 16 Sep 2025

Abstract

Background/Objectives: Identifying the optimal positive end-expiratory pressure (PEEP) is a major challenge in implementing strategies to prevent ventilator-induced lung injury in newborns. In this study, we assessed the validity of volumetric capnography based on the neonatal patient monitor (V_cap,PM) technique and [...] Read more.

Background/Objectives: Identifying the optimal positive end-expiratory pressure (PEEP) is a major challenge in implementing strategies to prevent ventilator-induced lung injury in newborns. In this study, we assessed the validity of volumetric capnography based on the neonatal patient monitor (V_cap,PM) technique and investigated the impact of PEEP on newborns. Methods: Analysis 1 evaluated the validity of the V_cap,PM technique with data from pediatric patients receiving invasive respiratory support. Linear regression and Bland–Altman analyses were performed on V_cap,PM and HAMILTON-C1 data. Analysis 2 evaluated the impact of PEEP on newborns. The PEEP level was increased from mild to high (the incremental phase) and then decreased from high to mild (the decremental phase) while performing the V_cap,PM technique on term and preterm infants. Results: Analysis 1 included 31 children (age, 9 [interquartile range (IQR), 0–36] months; weight, 6.0 [IQR, 3.8–10.5] kg). Regression and Bland–Altman analyses demonstrated the accuracy of V_cap,PM. Analysis 2 included 28 term (mean gestational age, 38 [IQR, 38–40] weeks; weight, 2924 [IQR, 2725–3109] g) and 21 preterm (mean gestational age, 33 [IQR, 31–34] weeks; weight, 1918 [IQR, 1356–2186] g) newborns. Despite no difference in tidal volume, high PEEP significantly increased airway dead space and decreased alveolar tidal volume compared to mild PEEP in each phase in term and preterm neonates. Conclusions: High PEEP induced airway dilation in newborns, as determined using a novel V_cap technique. This technique, which requires no special equipment, has the potential for wider clinical application in neonatal care. Full article

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

21 pages, 751 KB

Open AccessSystematic Review

Antenatal Sildenafil for Congenital Diaphragmatic Hernia: A Systematic Review and Bayesian Meta-Analysis of Preclinical Studies

by Tamara M. Hundscheid, Ilaria Amodeo, Giacomo Cavallaro, Carlijn R. Hooijmans, František Bartoš and Eduardo Villamor

Biomedicines 2025, 13(9), 2274; https://doi.org/10.3390/biomedicines13092274 - 16 Sep 2025

Abstract

Background: In congenital diaphragmatic hernia (CDH), pulmonary hypoplasia and pulmonary hypertension are major causes of morbidity and mortality. Antenatal treatment with sildenafil has shown some promising protective effects in experimental CDH, but no systematic review has yet evaluated the preclinical evidence on [...] Read more.

Background: In congenital diaphragmatic hernia (CDH), pulmonary hypoplasia and pulmonary hypertension are major causes of morbidity and mortality. Antenatal treatment with sildenafil has shown some promising protective effects in experimental CDH, but no systematic review has yet evaluated the preclinical evidence on this topic. Methods: PubMed and EMBASE databases were searched for studies using antenatal sildenafil in animal models of CDH. Bayesian model-averaged (BMA) meta-analysis was used to calculate Bayes factors (BFs). The BF₁₀ is the ratio of the probability of the data under the alternative hypothesis (presence of effect) over the probability of the data under the null hypothesis (absence of effect). Risk of bias was assessed by the SYRCLE tool. Results: We included 18 studies (14 nitrofen and 4 surgical CDH). The BMA analysis showed inconclusive evidence (BF₁₀ between 0.33 and 3) for the presence of an effect of sildenafil in fetal survival (7 studies, BF₁₀ = 1.25) or in lung hypoplasia as assessed by the lung-to-body weight ratio (16 studies, BF₁₀ = 2.04). In contrast, the BMA analysis showed conclusive evidence (BF₁₀ > 3) in favor of a positive effect of sildenafil on small pulmonary arteries medial wall thickness (12 studies, BF₁₀ = 1499), radial alveolar count (6 studies, BF₁₀ = 167.57), interalveolar septa thickness (4 studies, BF₁₀ = 56.86), distal airway complexity (3 studies, BF₁₀ = 7.95), mean saccular airspace diameter (2 studies, BF₁₀ = 7.61), total lung capacity (2 studies, BF₁₀ = 6.91), lung compliance (2 studies, BF₁₀ = 5.19), and VEGF expression (5 studies, BF₁₀ = 10.62). Conclusions: In preclinical models of CDH, antenatal sildenafil rescues pulmonary vascular remodeling and airway/airspace morphometric alterations. Full article

(This article belongs to the Special Issue Neonatal Disease: From Pathophysiology to Current and Emerging Therapeutic Approaches (2nd Edition))

11 pages, 811 KB

Open AccessArticle

ABCA1, ADIPOQ, APOE, FSTL4, and KCNQ1 Gene DNA Methylation Correlates with Lipid Profiles in Mexican Populations

by Karla E. Tello-Ortega, María A. Romero-Tlalolini, Angélica Martínez-Hernández, Elizabeth Ortiz-Sánchez, Cecilia Contreras-Cubas, Humberto García-Ortiz, Francisco Barajas-Olmos, Lorena Orozco and Federico Centeno

Biomedicines 2025, 13(9), 2273; https://doi.org/10.3390/biomedicines13092273 - 16 Sep 2025

Abstract

Background: Dyslipidemia, a significant modifiable risk factor for cardiovascular disease (CVD), represents a major global health challenge, particularly influenced by complex genetic and environmental interactions, mainly in indigenous populations. Methods: In this study, DNA samples from 80 individuals belonging to various indigenous [...] Read more.

Background: Dyslipidemia, a significant modifiable risk factor for cardiovascular disease (CVD), represents a major global health challenge, particularly influenced by complex genetic and environmental interactions, mainly in indigenous populations. Methods: In this study, DNA samples from 80 individuals belonging to various indigenous ethnic groups from northern and southern Mexico were analyzed to evaluate DNA methylation profiles and its correlation to lipid levels and other clinical parameters. Ten genes associated with metabolic changes were investigated using targeted bisulfite sequencing. Results: Our results revealed significant correlations between methylation in genes such as ABCA1, ADIPOQ, APOE, FSTL4, and KCNQ1 and clinical parameters including body mass index (BMI), lipid profiles, and body fat. Of the 151 CpG sites analyzed, 16 showed statistically significant correlations. Specifically, two ABCA1 CpGs sites correlated with BMI (p = 0.015) and triglycerides (p = 0.03); three ADIPOQ sites correlated with low-density lipoprotein cholesterol (LDLc) (p = 0.03, p = 0.005, p = 0.04, respectively); one APOE site correlated with BMI (p = 0.04), another with total cholesterol (p = 0.004) and triglycerides (p = 0.03) and two more with high-density lipoprotein cholesterol (HDLc) (p = 0.02 and p = 0.005, respectively); one FSTL4 CpG site with body fat (p = 0.02), another with total cholesterol (p = 0.02), one more with HDLc (p = 0.01), and another one with triglycerides (p = 0.01); and two KCNQ1 CpG sites correlated with body fat (p = 0.01 and p = 0.04, respectively). Conclusions: These findings show potential novel biomarkers for dyslipidemia risk. This research highlights the importance of understanding methylation changes in indigenous populations for developing personalized interventions and prevention strategies that could improve healthcare by linking epigenetic factors to CVD risk. Full article

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

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13 pages, 459 KB

Open AccessArticle

The Impact of Pulmonary Hypertension on Hospitalization Risk in Adults with Respiratory Syncytial Virus Infection

by Mayuri Mudgal, Aseem Rai Bhatnagar, Aneesh Kumar Vasudevan, Ajeetha Priya Gajendiran, Venkatesh Gondhi, Swetha Balaji, Shanjai Krishnan Murugan and Kulothungan Gunasekaran

Biomedicines 2025, 13(9), 2272; https://doi.org/10.3390/biomedicines13092272 - 16 Sep 2025

Abstract

Background/Objectives: Respiratory syncytial virus (RSV) infection can lead to significant complications, particularly among those with underlying cardiovascular and pulmonary complications. Patients with pulmonary hypertension (PH) are susceptible to clinical deterioration triggered by respiratory infections due to their limited cardiopulmonary reserve. This study [...] Read more.

Background/Objectives: Respiratory syncytial virus (RSV) infection can lead to significant complications, particularly among those with underlying cardiovascular and pulmonary complications. Patients with pulmonary hypertension (PH) are susceptible to clinical deterioration triggered by respiratory infections due to their limited cardiopulmonary reserve. This study aimed to assess the risk of hospitalization in RSV-infected adults with and without PH. Methods: We conducted a retrospective cohort study using the research network TriNetX to assess the risk of hospitalization in a cohort of patients with RSV infection, comparing those with and without PH. Propensity score matching was performed for demographic variables and RSV risk factors between the two cohorts. The risk of hospitalization was expressed as an adjusted odds ratio (aOR) with a 95% confidence interval (CI). Results: There were 193,256 patients in the RSV with PH cohort and 2,843,714 in the RSV without PH cohort (all aged >18 years). The mean age of the RSV with PH cohort was 68.2 ± 15.3 years, 50.6% were females, 64% were white, and 64.2% were group 2 PH. The RSV with PH cohort was at an increased risk of hospitalization (aOR 1.89, 95% CI 1.87–1.92, p-value 0.02). There was a significant risk (aOR 1.29, 95% CI 1.27–1.32) for the composite outcome of hospitalization-related complications between the two cohorts. Comorbid conditions (diabetes, cardiovascular disease, chronic lung disease, and chronic kidney disease) increased the risk of hospitalization in the RSV with PH group, with the biggest effect noted with underlying cardiovascular disease. Similarly, those with group 2 PH had a higher risk of hospitalization compared to the other PH groups. Remarkably, all PH groups demonstrated increased hospitalization risk compared to the RSV without PH cohort. Conclusions: We found that patients >18 years of age with PH and RSV infection were at an increased risk of hospitalization, with subsequently higher rates of RSV-infection-related complications. All PH groups had a higher hospitalization risk compared to the RSV without PH cohort, likely denoting PH as an independent risk factor for worse RSV-infection-related outcomes. RSV vaccination, therefore, may benefit all age groups of patients with PH. Full article

(This article belongs to the Special Issue New Insights in Respiratory Diseases)

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2 pages, 136 KB

Open AccessCorrection

Correction: Lee et al. Tumor-Associated Macrophages Affect the Tumor Microenvironment and Radioresistance via the Upregulation of CXCL6/CXCR2 in Hepatocellular Carcinoma. Biomedicines 2023, 11, 2081

by Hsin-Lun Lee, Yi-Chieh Tsai, Narpati Wesa Pikatan, Chi-Tai Yeh, Vijesh Kumar Yadav, Ming-Yao Chen and Jo-Ting Tsai

Biomedicines 2025, 13(9), 2271; https://doi.org/10.3390/biomedicines13092271 - 16 Sep 2025

Abstract

In the original publication [...] Full article

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

26 pages, 18774 KB

Open AccessArticle

Chitosan–Hydrazone-Modified Calcium Phosphate Scaffolds: Fabrication, Characterization, and Drug Delivery Potential

by Teodora Jakovljević, Jelena Stanisavljević, Julijana Stevanović, Miloš Petković, Ivana Z. Matić, Miloš Papić, Suzana Živanović, Tamara Matić, Vukašin Ugrinović, Djordje Janaćković, Biljana Ljujić and Djordje Veljović

Biomedicines 2025, 13(9), 2270; https://doi.org/10.3390/biomedicines13092270 - 15 Sep 2025

Abstract

Background/Objectives: Recent advancements in biomaterials aimed at closely mimicking natural biological tissues hold great promise for hard tissue regeneration and controlled drug release due to their superior physical, chemical, and biological properties. This study aimed to develop multi-ion doped calcium hydroxyapatite (HAp) [...] Read more.

Background/Objectives: Recent advancements in biomaterials aimed at closely mimicking natural biological tissues hold great promise for hard tissue regeneration and controlled drug release due to their superior physical, chemical, and biological properties. This study aimed to develop multi-ion doped calcium hydroxyapatite (HAp) scaffolds with chitosan-based coatings for localized drug delivery, incorporating a novel hydrazone compound with potential anticancer activity. Methods: HAp powders doped with magnesium (Mg²⁺), strontium (Sr²⁺), and varying fluoride (F⁻) contents (0–2 mol.%) were synthesized via a hydrothermal method. Scaffolds were fabricated using the sponge replica technique and subsequently coated with chitosan or a chitosan–hydrazone blend. Dopant incorporation was confirmed by electron dispersive X-ray spectroscopy (EDS). Phase composition and morphology were analyzed via X-ray diffraction (XRD) and scanning electron microscopy (SEM). Mechanical properties, bioactivity, cytotoxicity, and hydrazone release profiles were systematically evaluated. Results: EDS confirmed successful incorporation of Mg²⁺ and Sr²⁺ in all powders, while F⁻ was detected only in powders with 1 and 2 mol.% fluoride. XRD and SEM revealed the phase composition and scaffold microstructure. Chitosan coatings significantly improved scaffold compressive strength and reduced degradation rate, indicating enhanced stability in biological environments. The coated scaffolds supported MRC-5 fibroblast viability. The hydrazone compound exhibited dose-dependent antitumor cytotoxicity comparable to cisplatin and showed sustained release from scaffolds for up to 15 days. Conclusions: The combination of multi-ion doped HAp scaffolds and chitosan–hydrazone coatings provides a promising platform for bone tissue engineering and localized cancer therapy, demonstrating both mechanical stability and controlled, sustained drug release. Full article

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

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Graphical abstract

21 pages, 1236 KB

Open AccessArticle

The Usefulness of Peripheral and Organ Perfusion Monitoring in Predicting Mortality in Patients with Severe SARS-CoV-2

by Mateusz Gutowski, Arkadiusz Lubas, Bartosz Rustecki and Jakub Klimkiewicz

Biomedicines 2025, 13(9), 2269; https://doi.org/10.3390/biomedicines13092269 (registering DOI) - 15 Sep 2025

Abstract

Background: This study assessed whether repeated monitoring of peripheral and organ perfusion predicts mortality in severe SARS-CoV-2 patients. Methods: Peripheral perfusion was measured with finger oxygen saturation (SpO2), capillary refill time (CRT), and finger infrared thermography (FIT). Organ perfusion was measured [...] Read more.

Background: This study assessed whether repeated monitoring of peripheral and organ perfusion predicts mortality in severe SARS-CoV-2 patients. Methods: Peripheral perfusion was measured with finger oxygen saturation (SpO2), capillary refill time (CRT), and finger infrared thermography (FIT). Organ perfusion was measured with the color Doppler renal cortex perfusion (RCP) and Renal Cortical Resistive Index (RCRI). Patients with severe COVID-19 pneumonia were examined after a mean of 7 days of intensive treatment. Results: A total of 46 patients (16 women, 30 men, age 55.2 ± 12.7 years) completed the study. SpO2 and CRT emerged as independent key bedside indicators of prognosis, with an OR for death of 0.665 (CI 0.472–0.938) and 2.223 (CI 1.144–4.322). An SpO2 of 95% (sensitivity 58.3%, specificity of 64.7%) and CRT of ≥4 s (sensitivity 66.7%, specificity of 83.9%) were found as the best threshold values for the elevated risk of mortality. From estimated blood tests, only C-reactive proteins (OR 1.252, CI 1.023–1.542) and ferritin (OR 1.001, CI 1.000–1.002) were independently associated with mortality. Moreover, the elevation in CRP was a substantial death indicator (OR 1.707, CI 1.046–2.784). Conclusions: The estimation of peripheral perfusion using SpO2 and CRT after initial intensive treatment is helpful in the prediction of outcomes in patients with severe COVID-19. Full article

(This article belongs to the Special Issue Microbial Infections and Sepsis: Pathophysiological Mechanisms and Therapeutic Approaches)

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17 pages, 5356 KB

Open AccessArticle

Decoding TRIP13’s Role in Gastric Cancer: Implications for Prognosis and Immune Response

by Tongguo Shi, Yu Shen, Anjing Zhao, Rufang Dong, Fan Chen and Suhua Xia

Biomedicines 2025, 13(9), 2268; https://doi.org/10.3390/biomedicines13092268 - 15 Sep 2025

Abstract

Background/Objectives: Gastric cancer (GC), a prevalent global malignancy and a leading cause of cancer-related mortality, has a poorly understood prognosis related to TRIP13 expression. TRIP13 has a recognized part in driving tumor progression across different cancer types, yet its precise role in GC [...] Read more.

Background/Objectives: Gastric cancer (GC), a prevalent global malignancy and a leading cause of cancer-related mortality, has a poorly understood prognosis related to TRIP13 expression. TRIP13 has a recognized part in driving tumor progression across different cancer types, yet its precise role in GC remains beyond our full comprehension. Our study aimed to explore TRIP13’s prognostic value and function in GC patients. Methods: We extensively explored TRIP13’s influence on GC prognosis, functionality, and immune response by examining various cancer-related databases like UALCAN, GEPIA, GEO, and TIMER. Immunohistochemistry (IHC) staining was also conducted to assess the link between TRIM13 and GC patient survival. Results: TRIP13 expression levels were found to be significantly elevated in GC tissues compared to normal tissues through analysis of mRNA data from multiple public databases. IHC analysis exposed elevated TRIP13 protein levels in GC tissues and connected it with tumor depth. Prognostic evaluation demonstrated that GC patients exhibiting heightened TRIP13 expression endured a diminished overall survival rate. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses showed that genes related to TRIP13 are involved in processes such as the cell cycle and DNA repair. Additionally, TRIP13 expression was found to correlate with ferroptosis-related genes and may play a role in regulating ferroptosis. Immune cell infiltration analysis demonstrated that TRIP13 expression is negatively correlated with the infiltration of CD4⁺ T cells, CD8⁺ T cells, and B cells. Conclusions: TRIP13 emerges as a candidate independent prognostic indicator and a promising intervention point for GC treatment. Full article

(This article belongs to the Section Immunology and Immunotherapy)

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10 pages, 1451 KB

Open AccessArticle

The Effect of Neurorehabilitation of the Cognitive Symptoms of Long COVID Evaluated with Neuropsi Atención y Memoria-III and BANFE-III

by Ana Lilia Dotor-Llerena, Samuel Reyes-Long, Leilani Najera-García, Sandra Hernández-Corral, Elena Arechaga-Ocampo, Karina Avendaño-Ortiz, David Trejo-Martínez, Humberto Rosell-Becerril, Jose Luis Cortes-Altamirano and Alfonso Alfaro-Rodríguez

Biomedicines 2025, 13(9), 2267; https://doi.org/10.3390/biomedicines13092267 - 15 Sep 2025

Abstract

Background: The long-haul symptoms of COVID-19 have not been properly attended, especially those of the central nervous system. Attention, memory and executive functioning are the three main cognitive symptoms reported for long COVID patients. To this day, neurorehabilitation therapy to alleviate these [...] Read more.

Background: The long-haul symptoms of COVID-19 have not been properly attended, especially those of the central nervous system. Attention, memory and executive functioning are the three main cognitive symptoms reported for long COVID patients. To this day, neurorehabilitation therapy to alleviate these symptoms has not been proposed. Objectives: The current study aims to evaluate the effect of a neurorehabilitation intervention on the three most prevalent symptoms reported for long COVID in Mexican patients: memory, attention and executive functioning. Methods: Subjects were recruited at Instituto Nacional de Rehabilitación Luis Guillermo Ibarra Ibarra and underwent a novel neurorehabilitation intervention for 6 months. Baseline measurements were taken using validated instruments (Neuropsi, BANFE and CCQ) before the intervention and after it. Results: A significant decrease in the normalized score of the Memory component of the Neuropsi Atención y Memoria III test was found after the intervention, along with a decrease in two components of the BANFE-III test. Conclusions: In the current study, a successful neuropsychology intervention for the main cognitive symptoms of long COVID in a Mexican population reduced subjective self-perceived complaints and objectively measured cognitive symptoms. Full article

(This article belongs to the Special Issue Latest Research in Post-COVID (Long COVID): Pathological and Treatment Studies of Sequelae and Complications—3rd Edition)

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21 pages, 790 KB

Open AccessSystematic Review

The Use of Platelet-Rich Fibrin in Combination with Synthetic Bone Grafting: A Systematic Review

by Rosana Costa, Alicia Carvalho, Paula López-Jarana, Vitória Costa, Marta Relvas, Filomena Salazar, Tomás Infante da Câmara, Miguel Nunes Vasques and Marco Infante da Câmara

Biomedicines 2025, 13(9), 2266; https://doi.org/10.3390/biomedicines13092266 - 15 Sep 2025

Abstract

Background: In atrophic posterior maxillary regions, sub-antral surgery is often used for rehabilitation with implants. In order to stimulate bone regeneration, autogenous, xenogenic, alloplastic and platelet-rich fibrin (PRF) grafts are commonly used. Aim: To assess the effectiveness of PRF alone or combination with [...] Read more.

Background: In atrophic posterior maxillary regions, sub-antral surgery is often used for rehabilitation with implants. In order to stimulate bone regeneration, autogenous, xenogenic, alloplastic and platelet-rich fibrin (PRF) grafts are commonly used. Aim: To assess the effectiveness of PRF alone or combination with synthetic bone substitutes on bone formation, implant stability, and survival in sub-antral surgery. Materials and Methods: A literature review was carried out from September 2024 to April 2025, according to PRISMA guidelines using the PubMed, Cochrane Library, Wiley, ScienceDirect, and Web of Science databases. From a total of 601 articles identified, 11 met the inclusion criteria and were selected for analysis. Results: PRF in combination with synthetic materials has shown potential benefits, especially in increasing biomechanical stability and bone formation. Although, most studies have not reported statistically significant differences when comparing the use of synthetic material alone against its combination with PRF. Discussion: The use of synthetic grafts in combination with PRF has become increasingly common in sub-antral implant procedures. PRF promotes angiogenesis, osteoprogenitor cell differentiation and bone regeneration, favouring the healing and remodelling process of the tissues, as well as greater stability and longevity of the implant. Conclusions: The combination of PRF with synthetic bone grafting shows promising results; however, further studies are needed to confirm the efficacy of PRF in maxillary sinus grafts in conjunction with the use of biomaterials. Full article

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

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