Biomedicines

0 pages, 153 KiB

Open AccessCorrection

Correction: Al-Lahham et al. Reference Interval for Glycated Albumin, 1,5-AG/GA, and GA/HbA1c Ratios and Cut-Off Values for Type 1, Type 2, and Gestational Diabetes: A Cross-Sectional Study. Biomedicines 2024, 12, 2651

by Yusra Al-Lahham, Waldemar Volanski, Liana Signorini, Ademir Luiz do Prado, Glaucio Valdameri, Vivian Rotuno Moure, Marciane Welter, Alexessander C. Alves, Marcel Henrique Marcondes Sari, Fabiane Gomes de Moraes Rego and Geraldo Picheth

Biomedicines 2025, 13(7), 1621; https://doi.org/10.3390/biomedicines13071621 - 2 Jul 2025

Abstract

In the original publication [...] Full article

(This article belongs to the Special Issue Biomarkers in Metabolic Disorders, Obesity and Type 2 Diabetes Mellitus)

15 pages, 261 KiB

Open AccessArticle

Variations in Prehospital Analgesic Use Based on Pain Etiology

by Nikolina Marić, Radojka Jokšić-Mazinjanin, Aleksandar Đuričin, Luka Ivanišević, Goran Rakić, Zoran Gojković, Mirka Lukić Šarkanović, Milena Jokšić Zelić, Lucija Vasović and Velibor Vasović

Biomedicines 2025, 13(7), 1620; https://doi.org/10.3390/biomedicines13071620 - 1 Jul 2025

Abstract

Background/Objectives: Pain is the most frequently reported symptom in over 90% of patients presenting with traumatic injuries, and three-quarters of patients are discharged from emergency departments experiencing moderate to severe pain. The objective of this study was to compare the frequency of [...] Read more.

Background/Objectives: Pain is the most frequently reported symptom in over 90% of patients presenting with traumatic injuries, and three-quarters of patients are discharged from emergency departments experiencing moderate to severe pain. The objective of this study was to compare the frequency of analgesic administration between patients with chest pain presumed to be of cardiac origin and those with suspected bone fractures as well as to assess whether significant differences exist between these two groups. Methods: A retrospective, observational study was conducted. Patients were categorized into two groups: Group 1—patients with angina pectoris, acute myocardial infarction, or non-specific chest pain; and Group 2—patients with a preliminary diagnosis of bone fracture made by the attending physician at the scene. Results: A total of 1189 patients were included in this study, with 503 (42.3%) in Group 1 and 686 (57.7%) in Group 2 (χ² = 28.166; p < 0.001). Analgesic administration was significantly more frequent among patients in Group 1 than in Group 2 (χ² = 23.187; p < 0.001). Within Group 1, the highest rate of analgesic use was recorded in patients diagnosed with acute myocardial infarction. In Group 2, analgesics were administered to 36.4% of patients with suspected trunk bone fractures, while only 7.1% of patients with suspected cranial fractures received analgesic therapy. Pain intensity scores were not available for either group. Conclusions: The administration of analgesic treatment was significantly more common among patients presenting with chest pain of presumed cardiac origin than among those with suspected bone fractures, including fractures involving multiple body regions. Full article

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

16 pages, 560 KiB

Open AccessReview

Comprehensive Review: Mavacamten and Aficamten in Hypertrophic Cardiomyopathy

by Helin Savsin and Tomasz Tokarek

Biomedicines 2025, 13(7), 1619; https://doi.org/10.3390/biomedicines13071619 - 1 Jul 2025

Abstract

Hypertrophic cardiomyopathy (HCM) is the most common monogenic heart disease, with an estimated prevalence of 1:600 in the general population, and is associated with significant morbidity. HCM is characterized by left ventricular hypertrophy and interventricular septal thickening due to sarcomere protein gene mutations. [...] Read more.

Hypertrophic cardiomyopathy (HCM) is the most common monogenic heart disease, with an estimated prevalence of 1:600 in the general population, and is associated with significant morbidity. HCM is characterized by left ventricular hypertrophy and interventricular septal thickening due to sarcomere protein gene mutations. The recent emergence of cardiac myosin inhibitors (CMIs), specifically mavacamten and aficamten, has introduced a paradigm shift in HCM management by directly targeting the hypercontractile state of the disease. This review comprehensively discusses the molecular mechanisms of mavacamten and aficamten, highlighting their biochemical similarities and differences from available data. It evaluates their reported efficacy in completed clinical trials, such as reducing left ventricular outflow tract (LVOT) obstruction, improving functional capacity, and enhancing quality of life in HCM. It further provides insight and updates to ongoing trials of both CMIs. Finally, it compares and elaborates on the safety profiles of mavacamten and aficamten, discussing their favorable safety profiles shown in completed studies. In current clinical practice, only mavacamten is approved for use, and clinical insights concerning both CMIs are limited, but encouraging. In summary, cardiac myosin inhibitors are a promising class of disease-modifying drugs for HCM with proven short-term safety and efficacy, but limited data are available to fully determine their long-term effects and efficacy in diverse patient populations. Ongoing research is necessary to further explore and define their role in HCM management. Full article

(This article belongs to the Special Issue Progress in Cardiovascular Pharmacology)

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21 pages, 858 KiB

Open AccessReview

Hepato-Renal Crosstalk in Acute and Chronic Disease: From Shared Pathways to Therapeutic Targets

by Anna Clementi, Grazia Maria Virzì, Massimiliano Sorbello, Nenzi Marzano, Paola Monciino, Jose Said Cabrera-Aguilar, Giovanni Giorgio Battaglia, Claudio Ronco and Monica Zanella

Biomedicines 2025, 13(7), 1618; https://doi.org/10.3390/biomedicines13071618 - 1 Jul 2025

Abstract

Hepato-renal crosstalk is a complex biological communication between liver and kidneys mediated by various factors, including cellular, endocrine, and paracrine molecules. This interaction highlights the functional consequences that damage in one organ can have on the other. In particular, the liver and kidney [...] Read more.

Hepato-renal crosstalk is a complex biological communication between liver and kidneys mediated by various factors, including cellular, endocrine, and paracrine molecules. This interaction highlights the functional consequences that damage in one organ can have on the other. In particular, the liver and kidney play a pivotal role in maintaining body homeostasis, as they are both involved in the excretion of toxic bioproducts and drugs. The overlap of liver and kidney disease has both therapeutic and prognostic implications. Therefore, a better understanding of the mechanisms involved in the pathogenesis of this bidirectional crosstalk is essential for improving the management of these clinical conditions and patient outcomes. Specifically, a multidisciplinary approach involving hepatologists and nephrologists is crucial to reduce the long-term burden of these clinical settings. This review focuses on the hepato-renal crosstalk in the context of liver and kidney disease, with particular attention to acute kidney injury associated with liver injury, hepatorenal syndrome and, chronic kidney disease in the context of liver fibrosis. Full article

(This article belongs to the Special Issue New Insights in the Pathogenesis and Treatment of Chronic Kidney Disease and Its Complications)

10 pages, 793 KiB

Open AccessArticle

The Pleiotropic Effect of ANRIL in Glaucoma and Cardiovascular Disease

by Luke O’Brien, Daire J. Hurley, Michael O’Leary, Liam Bourke and Colm O’Brien

Biomedicines 2025, 13(7), 1617; https://doi.org/10.3390/biomedicines13071617 - 1 Jul 2025

Abstract

Background/Objectives: The INK4 locus at chromosome 9p21.3, encoding CDKN2A, CDKN2B and the long non-coding RNA CDKN2B-AS1 (ANRIL), has been implicated in multiple diseases, including glaucoma and cardiovascular disease. ANRIL plays a critical role in gene regulation, inflammation and cell proliferation, contributing to [...] Read more.

Background/Objectives: The INK4 locus at chromosome 9p21.3, encoding CDKN2A, CDKN2B and the long non-coding RNA CDKN2B-AS1 (ANRIL), has been implicated in multiple diseases, including glaucoma and cardiovascular disease. ANRIL plays a critical role in gene regulation, inflammation and cell proliferation, contributing to disease susceptibility through shared molecular mechanisms. This study aims to identify SNPs within the INK4 locus associated with both glaucoma and CVD using the Open Targets Genetics platform and assess their pleiotropic effects. Methods: We utilised the Open Targets Genetics platform to identify SNPs at the INK4 locus associated with glaucoma and CVD. For each SNP, we recorded its genomic location, statistical significance and associated phenotypes. We further analysed the SNPs using the Genome Aggregation Database (gnomAD) to confirm their genomic position. Phenotypic associations were assessed using PheWAS data. Results: We identified 20 GWAS SNPs significantly associated with both glaucoma and CVD. All SNPs were located within intronic regions of the long non-coding RNA ANRIL. Certain SNPs such as rs4977756, rs1333037 and rs1063192 have known pleiotropic effects, influencing retinal ganglion cell survival in glaucoma and vascular smooth muscle cell proliferation in CVD. These SNPs influence shared biological pathways, including inflammation, oxidative stress and epigenetic regulation, and may exert either protective or pathogenic effects. Certain SNPs such as rs7853090 and rs1434537531 remain underexplored, emphasising the need for further research. Conclusions: This study highlights the pleiotropic role of ANRIL in glaucoma and CVD, driven by shared genetic and molecular pathways. While SNPs within ANRIL provide valuable insights into disease mechanisms, these conditions remain complex, influenced by multiple genetic and environmental factors. Targeting ANRIL therapeutically poses challenges due to its non-coding nature, but emerging RNA-based therapies, including antisense oligonucleotides and small-molecule modulators, hold promise. Further research into underexplored SNPs and ANRIL’s regulatory mechanisms is essential for advancing therapeutic development and understanding these multifactorial diseases. Full article

(This article belongs to the Special Issue Feature Reviews in Ophthalmology)

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11 pages, 2253 KiB

Open AccessArticle

PPARgamma Modulates CD4⁺ T-Cell Differentiation and Allergic Inflammation in Allergic Rhinitis: A Potential Therapeutic Target

by Xiaoqing Rui, Suyu Ruan, Yu Zhang, Ranran Fu, Pengfei Sun, Danzeng Lamu and Weihua Wang

Biomedicines 2025, 13(7), 1616; https://doi.org/10.3390/biomedicines13071616 - 1 Jul 2025

Abstract

Objectives: Given the emerging role of peroxisome proliferator-activated receptor gamma (PPARgamma) in immune regulation and the increasing prevalence of allergic rhinitis (AR), we sought to understand how modulation of the PPARgamma pathway impacts the balance of CD4⁺ T-cell subsets, particularly [...] Read more.

Objectives: Given the emerging role of peroxisome proliferator-activated receptor gamma (PPARgamma) in immune regulation and the increasing prevalence of allergic rhinitis (AR), we sought to understand how modulation of the PPARgamma pathway impacts the balance of CD4⁺ T-cell subsets, particularly regulatory T cells (Tregs) and T helper (TH)1, TH2, and TH17 cells, which are key players in the pathogenesis of AR. This knowledge is crucial for developing novel therapeutic strategies targeting the PPARgamma-CD4⁺ T-cell axis to manage AR more effectively. Methods: We used PPARgamma^f/fLyz2-Cre mice for PPARgamma deletion. In an ovalbumin (OVA)-induced AR mouse model, PPARgamma^+/-f/fLyz2-Cre mice were assessed for allergic symptoms, splenic Tregs, and nasal eosinophils. Additionally, the effects of a PPARgamma agonist on the polarization of naïve CD4⁺ T cells were examined. Results: PPARgamma^+/-f/fLyz2-Cre mice showed worsened allergic symptoms, reduced splenic Tregs, and increased nasal mucosa eosinophilic infiltration. PPARgamma agonist treatment promoted naïve CD4⁺ T-cell polarization into Tregs and inhibited their differentiation into TH1, TH2, and TH17 subsets. Conclusions: Our findings indicate that PPARgamma plays a crucial role in regulating TH-cell subsets in AR. PPARgamma agonists could be a potential therapeutic strategy to mitigate allergic inflammation in AR by promoting Treg development and suppressing pathogenic TH-cell responses. Full article

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

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16 pages, 2212 KiB

Open AccessArticle

Long COVID and Its Impacts: A Case–Control Study in Brazil

by Cristina M. Ruas, Maria Laura Silva, Ana L. G. F. Figueiredo, Amanda P. de Alencar, Samuel de S. Melo, Geovani F. de Castro, Natália V. Carobin, Melina A. Cordeiro, Janete F. R. Aguirre, Amanda F. M. de Oliveira and Adriano de P. Sabino

Biomedicines 2025, 13(7), 1615; https://doi.org/10.3390/biomedicines13071615 (registering DOI) - 1 Jul 2025

Abstract

Introduction: Long COVID, or post-COVID-19 syndrome, refers to a set of persistent symptoms following SARS-CoV-2 infection without another identifiable cause. Studies indicate that symptoms can last for up to two years and affect multiple body systems. Objective: The objective of this study is [...] Read more.

Introduction: Long COVID, or post-COVID-19 syndrome, refers to a set of persistent symptoms following SARS-CoV-2 infection without another identifiable cause. Studies indicate that symptoms can last for up to two years and affect multiple body systems. Objective: The objective of this study is to compare symptom prevalence between infected individuals pre and post-COVID-19 and non-infected individuals in a population from Southeastern Brazil. Materials and Methods: A case–control study was conducted with participants from the MonitoraCovid program in a university in Brazil. The study included adults who responded to a questionnaire about long COVID symptoms. Data were collected virtually between October 2023 and May 2024. Results: Of the 2886 individuals eligible for analysis, 75.5% reported having been positive for COVID-19. Most participants were vaccinated, with 82.99% receiving two doses. In the pre and post comparison, individuals who had COVID-19 were more likely to report increased symptoms after infection, with 95.5% of assessed conditions worsening, particularly cognitive and respiratory issues. A comparison between those who had and had not been infected with COVID-19 showed that only 6.67% of symptoms were more prevalent in the infected group. The most significant post-COVID-19 symptoms included memory problems, fatigue, and shortness of breath, though some conditions, such as anxiety and sleep disturbances, were less common among those who had COVID-19. Conclusions: The findings reinforce that long COVID significantly impacts cognitive health, highlighting the importance of monitoring previously infected individuals. The study also emphasizes the need for further research in Global South contexts to better understand the long-term implications of COVID-19. 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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16 pages, 246 KiB

Open AccessArticle

Severe Traumatic Brain Injuries and Associated Outcomes at a Level 1 Trauma Center

by Bharti Sharma, Tirth Patel, Hasan Al-Ali, George Agriantonis, Navin D. Bhatia, Carrie Garcia, Praise Nesamony, Jasmine Dave, Juan Mestre, Shalini Arora, Saad Bhatti, Zahra Shafaee, Suganda Phalakornkul, Kate Twelker and Jennifer Whittington

Biomedicines 2025, 13(7), 1614; https://doi.org/10.3390/biomedicines13071614 - 1 Jul 2025

Abstract

Background: Severe traumatic brain injury (TBI) remains a leading cause of mortality and long-term morbidity, particularly in high-acuity trauma settings. We aim to evaluate the clinical, physiologic, and socioeconomic factors associated with outcomes in patients with severe traumatic brain injury (TBI) at a [...] Read more.

Background: Severe traumatic brain injury (TBI) remains a leading cause of mortality and long-term morbidity, particularly in high-acuity trauma settings. We aim to evaluate the clinical, physiologic, and socioeconomic factors associated with outcomes in patients with severe traumatic brain injury (TBI) at a single urban Level 1 trauma center. Method: This is a single-center, retrospective study of patients presenting with severe TBI between 1 January 2020 and 31 December 2023 at Elmhurst Hospital Center in Queens, New York. Patients were identified using ICD trauma codes and an Abbreviated Injury Severity (AIS) Head score of ≥3. Demographic data, injury characteristics, vital signs, airway interventions, alcohol level, and insurance status were analyzed. Result: A total of 1130 patients met the inclusion criteria. The cohort was predominantly male (76.1%) with a mean age of 52.7 years. Blunt trauma accounted for 97.8% of cases, with a mortality rate of 13.8%, while penetrating trauma comprised 2.2%, with a markedly higher mortality rate of 48%. Patients who died as full code had lower mean systolic blood pressure (82.5 mmHg), oxygen saturation (63%), and shorter emergency department stays (~3.7 h). The mean Glasgow Coma Scale (GCS) score was 12.6, dropping to 6.0 in patients who died. Moreover, higher AIS Head and Injury Severity Score (ISS) values were correlated with worse outcomes. Severely intoxicated patients had higher TBI incidence, with no clear difference observed when compared to normal BAC levels. Self-pay patients exhibited the highest mortality (40%). All associations were statistically significant (p < 0.0001). Conclusions: Severe TBI outcomes are significantly influenced by injury mechanisms, physiologic parameters, and socioeconomic status. These findings emphasize the need for targeted prognostic tools and improved trauma system preparedness for TBI patients at risk of poor outcomes. Full article

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

20 pages, 1773 KiB

Open AccessReview

Beyond Muscle Weakness: Unraveling Endocrine and Metabolic Dysfunctions in DMD, a Narrative Review

by Giuseppe Cannalire, Giacomo Biasucci, Vanessa Sambati, Tommaso Toschetti, Arianna Maria Bellani, Anna-Mariia Shulhai, Federica Casadei, Erika Rita Di Bari, Francesca Ferraboschi, Cecilia Parenti, Maria Carmela Pera, Susanna Esposito and Maria Elisabeth Street

Biomedicines 2025, 13(7), 1613; https://doi.org/10.3390/biomedicines13071613 - 1 Jul 2025

Abstract

Background: Duchenne muscular dystrophy (DMD) is a severe X-linked neuromuscular disorder caused by mutations in the DMD gene, leading to progressive muscle degeneration, loss of ambulation, and multi-systemic complications. Beyond its impact on mobility, DMD is associated with significant endocrine and metabolic dysfunctions [...] Read more.

Background: Duchenne muscular dystrophy (DMD) is a severe X-linked neuromuscular disorder caused by mutations in the DMD gene, leading to progressive muscle degeneration, loss of ambulation, and multi-systemic complications. Beyond its impact on mobility, DMD is associated with significant endocrine and metabolic dysfunctions that develop over time. Objective: To provide a comprehensive analysis of growth disturbances, endocrine dysfunctions, and metabolic complications in DMD including bone metabolism, considering the underlying mechanisms, clinical implications, and management strategies for daily clinical guidance. Methods: In this narrative review, an evaluation of the literature was conducted by searching the Medline database via the PubMed, Scopus, and Web of Science interfaces. Results: Growth retardation is a hallmark feature of DMD, with patients exhibiting significantly shorter stature compared to their healthy peers. This is exacerbated by long-term glucocorticoid therapy, which disrupts the growth hormone/insulin-like growth factor-1 (GH/IGF-1) axis and delays puberty. Obesity prevalence follows a biphasic trend, with increased risk in early disease stages due to reduced mobility and corticosteroid use, followed by a decline in body mass index (BMI) in later stages due to muscle wasting. Metabolic complications, including insulin resistance, altered lipid metabolism, and hepatic steatosis, further characterize disease burden. Osteoporosis and increased fracture risk, primarily due to reduced mechanical loading and glucocorticoid-induced bone resorption, are major concerns, needing early screening and intervention. The RANK/RANKL/OPG signaling pathway has emerged as a critical factor in bone deterioration, providing potential therapeutic targets for improving skeletal health. Conclusions: Growth and endocrine disorders in DMD are complex and multifactorial, requiring proactive monitoring and early intervention. Addressing these issues requires a multidisciplinary approach integrating endocrine, nutritional, and bone health management. Further research is essential to refine treatment strategies that mitigate growth and metabolic disturbances while preserving overall patient well-being. Full article

(This article belongs to the Special Issue Musculoskeletal Diseases: From Molecular Basis to Therapy (Volume II))

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10 pages, 1164 KiB

Open AccessArticle

Myocardial Damage Patterns in Patients with Left Ventricular Systolic Dysfunction with and Without Coronary Artery Disease Referred for Cardiac Magnetic Resonance

by Justyna M. Sokolska, Katarzyna Logoń, Magdalena Pszczołowska and Wojciech Kosmala

Biomedicines 2025, 13(7), 1612; https://doi.org/10.3390/biomedicines13071612 - 1 Jul 2025

Abstract

Background: Cardiac magnetic resonance (CMR) is widely used to determine the underlying cause of left ventricular (LV) systolic dysfunction. Patients with ischemic disease are less frequently referred for CMR, as the underlying disease is often presumed to explain LV systolic dysfunction. However, [...] Read more.

Background: Cardiac magnetic resonance (CMR) is widely used to determine the underlying cause of left ventricular (LV) systolic dysfunction. Patients with ischemic disease are less frequently referred for CMR, as the underlying disease is often presumed to explain LV systolic dysfunction. However, various etiologies of myocardial impairment may coexist. Late gadolinium enhancement (LGE) is a technique used for tissue characterization, particularly visualization of myocardial fibrosis. Objectives: The aim of this study was to assess the prevalence of LGE patterns suggesting ischemic or non-ischemic etiology of myocardial damage in patients with LV systolic dysfunction with and without known coronary artery disease (CAD). Methods: 131 patients (76% male, 55 ± 15 years old) with LV ejection fraction (LVEF) ≤ 50% in echocardiography underwent CMR between December 2021 and November 2022. Patients were divided according to the known history of CAD. Regional subendocardial and transmural LGE was interpreted as ischemic etiology, whereas midmyocardial and subepicardial LGE was non-ischemic. Results: The mean LVEF assessed in CMR was 35 ± 10%. A total of 122 patients underwent CMR with LGE sequence. LGE was detected in 62% of patients: 34% had a non-ischemic pattern, 16% ischemic, and 11% mixed. LGE patterns did not differ between patients with and without CAD. In every third patient with CAD and almost every second patient without CAD, no myocardial fibrosis was detected. A completely normal CMR study was found in 6% of patients without CAD and 1% of patients with CAD (all p NS). Conclusions: The LGE patterns suggesting ischemic or non-ischemic myocardial damage are similarly prevalent in patients with and without known CAD. The diagnosis based solely on clinical information may be unreliable, as LV dysfunction might have multifactorial origins. The absence of local myocardial fibrosis is relatively common in patients with LV dysfunction, irrespective of its etiology. Full article

(This article belongs to the Special Issue Acute and Chronic Heart Failure: Pathophysiology and New Therapeutic Developments, 2nd Edition)

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23 pages, 8434 KiB

Open AccessArticle

Duodenal Adenocarcinoma Is Characterized by Acidity, High Infiltration of Macrophage, and Activated Linc01559–GRSF1 Axis

by Xinxin Huang, Ying Shi, Zekun Liu, Yihang Wu, Xiaotong Luo, Dongwen Chen, Zhengyu Wei, Chong Chen, Huaiqiang Ju, Xiaojian Wu, Xuanhui Liu, Zhanhong Chen and Peishan Hu

Biomedicines 2025, 13(7), 1611; https://doi.org/10.3390/biomedicines13071611 - 30 Jun 2025

Abstract

Background: Duodenal adenocarcinoma (DA) is often insidious due to the low rate of early diagnosis and because the mechanisms that underlie its malignant progression are poorly understood. The tumor microenvironment (TME) plays a crucial regulatory role in promoting tumor malignancy. Hence, this [...] Read more.

Background: Duodenal adenocarcinoma (DA) is often insidious due to the low rate of early diagnosis and because the mechanisms that underlie its malignant progression are poorly understood. The tumor microenvironment (TME) plays a crucial regulatory role in promoting tumor malignancy. Hence, this study aimed to identify novel biomarkers for early diagnosis and potential therapeutic targets for DA. Methods: Surgical resection samples and normal tissues from DA patients were collected for RNA sequencing (RNA-seq). The characteristics of TME in DA patients were analyzed, and the differentially expressed long non-coding RNAs (lncRNA) were screened. Functional experiments were performed to verify the relationship between Linc01559, G-rich sequence binding factor 1 (GRSF1), and tumor malignant phenotype. Results: The present study revealed that DA exhibits a significantly upregulated expression of acidic environment markers and a high degree of macrophage infiltration. Further investigation revealed that macrophages upregulate the expression of the long noncoding RNA, Linc01559, in DA through the STAT3/c-MYC signaling pathway, thereby promoting malignant phenotypes such as invasion, metastasis, tumor stemness, and apoptosis. The interaction between GRSF1 and Linc01559 was subsequently confirmed using RNA pulldown-mass spectrometry. It was further revealed that Linc01559 promotes the malignant phenotype of duodenal cancer cells through its interaction with GRSF1. Conclusions: These findings demonstrate that the acidic microenvironment influences the phenotype of DA by regulating the Linc01559–GRSF1 axis. Therefore, these findings provide potential targets for the early detection and treatment of DA. Full article

(This article belongs to the Special Issue Genomic Insights and Translational Opportunities for Human Cancers)

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27 pages, 1132 KiB

Open AccessReview

GLP-1 and Its Role in Glycogen Production: A Narrative Review

by Joseph Lotosky, Xavier Jean, Anungoo Altankhuyag, Saqib Khan, Ashley Bernotas, Alireza Sharafshah, Kenneth Blum, Alan Posner and Panayotis K. Thanos

Biomedicines 2025, 13(7), 1610; https://doi.org/10.3390/biomedicines13071610 - 30 Jun 2025

Abstract

Glucagon-like peptide-1 (GLP-1) has emerged as a pivotal regulator in the management of glucose homeostasis, glycogen metabolism, and energy balance, positioning it as a critical therapeutic target for addressing obesity, metabolic syndrome, and type 2 diabetes mellitus (T2DM). GLP-1 receptor agonists (GLP-1RAs) have [...] Read more.

Glucagon-like peptide-1 (GLP-1) has emerged as a pivotal regulator in the management of glucose homeostasis, glycogen metabolism, and energy balance, positioning it as a critical therapeutic target for addressing obesity, metabolic syndrome, and type 2 diabetes mellitus (T2DM). GLP-1 receptor agonists (GLP-1RAs) have shown promise for improving glycemic control and reducing weight through appetite regulation, delayed gastric emptying, and energy expenditure modulation. This narrative review explores the mechanisms of GLP-1-mediated glycogen metabolism and energy expenditure, particularly in key tissues—pancreas, liver, skeletal muscle, and adipose tissue. In the pancreas, GLP-1 enhances insulin secretion and beta-cell function. In the liver, it promotes glycogen synthesis via insulin-dependent and potential insulin-independent pathways, involving protein kinase B (AKT) and AMP-activated protein kinase (AMPK) signaling. Skeletal muscle benefits from GLP-1 through increased glucose uptake, AMPK activation, and mitochondrial function, facilitating glycogen storage. In adipose tissue, GLP-1 stimulates brown adipose tissue (BAT) thermogenesis and energy expenditure, contributing to weight loss. This increase in energy expenditure, along with enhanced glycogen metabolism, is a plausible mechanism for the weight loss observed with GLP-1RAs. Despite these advances, significant knowledge gaps remain, particularly regarding the direct hepatic effects of GLP-1, the extent to which it modulates glycogen metabolism in vivo, and its impact on thermogenesis in humans. Future research focusing on both the tissue-specific actions of GLP-1 and its systemic role in energy homeostasis and metabolic regulation will be essential for optimizing its therapeutic potential. Full article

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

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12 pages, 708 KiB

Open AccessArticle

Venetoclax-Based Regimens in CLL: Immunoglobulin G Levels, Absolute Neutrophil Counts, and Infectious Complications

by Wojciech Szlasa, Monika Kisielewska, Anna Sobczyńska-Konefał, Emilia Jaskuła, Monika Mordak-Domagała, Jacek Kwiatkowski, Katarzyna Tatara, Agnieszka Kuś, Mateusz Sawicki, Izabela Dereń-Wagemann, Mariola Sędzimirska, Ugo Giordano and Jarosław Dybko

Biomedicines 2025, 13(7), 1609; https://doi.org/10.3390/biomedicines13071609 - 30 Jun 2025

Abstract

Background: Chronic lymphocytic leukemia (CLL) is a prevalent hematologic malignancy that predominantly affects elderly individuals, posing significant clinical challenges due to patient comorbidities and inherent resistance to conventional chemotherapy. The emergence of targeted therapies combining venetoclax, a selective inhibitor of the anti-apoptotic protein [...] Read more.

Background: Chronic lymphocytic leukemia (CLL) is a prevalent hematologic malignancy that predominantly affects elderly individuals, posing significant clinical challenges due to patient comorbidities and inherent resistance to conventional chemotherapy. The emergence of targeted therapies combining venetoclax, a selective inhibitor of the anti-apoptotic protein BCL-2, with anti-CD20 monoclonal antibodies has dramatically transformed the treatment landscape. Methods: This retrospective observational study analyzed the differential impacts of first-line venetoclax-obinutuzumab (VenO) and second-line venetoclax-rituximab (VenR) on immunoglobulin G (IgG) levels and absolute neutrophil count (ANC) in CLL patients. Results: Our findings indicate that during first-line VenO therapy, a significant improvement in ANC levels from baseline was observed, whereas patients undergoing second-line VenR therapy demonstrated limited impact on ANC and the decreasing tendency in IgG levels. Patients treated with VenR had a longer disease history and previous exposure to other treatment regimens, primarily chemoimmunotherapy, which could negatively influence immune recovery, making direct comparisons between these two treatment lines challenging. Although this observational study did not directly compare infection rates, the observed enhancement of ANC levels in patients receiving VenO suggests a potential for lower infection risk compared to pretreated VenR patients. Conclusions: These results underscore the clinical significance of considering both the treatment line and the patient’s prior therapeutic history when selecting venetoclax-based regimens for CLL. The potential association of first-line VenO with improved immunological parameters and the complex impact of prior therapies on immunological recovery with second-line VenR warrant further prospective investigation into the correlation between treatment regimen, patient history, immune function, and infectious complications. Full article

(This article belongs to the Special Issue Innovative Approaches to Molecular Pathogenesis and Therapy of Lymphoid Malignancies)

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17 pages, 4114 KiB

Open AccessArticle

Proteomic Profiling Reveals TPR and FGA as Predictive Serum Biomarkers of Relapse to First- and Second-Generation EGFR-TKIs in Advanced Lung Adenocarcinoma

by Pritsana Raungrut, Wararat Chiangjong, Thipphanet Masjon, Saowanee Maungchanburi, Thidarat Ruklert and Narongwit Nakwan

Biomedicines 2025, 13(7), 1608; https://doi.org/10.3390/biomedicines13071608 - 30 Jun 2025

Abstract

Background: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) significantly enhance the median survival of patients with lung adenocarcinoma (ADC) that harbor EGFR-sensitive mutations. However, most patients inevitably experience tumor relapse owing to drug resistance. We aimed to identify potential serum biomarkers [...] Read more.

Background: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) significantly enhance the median survival of patients with lung adenocarcinoma (ADC) that harbor EGFR-sensitive mutations. However, most patients inevitably experience tumor relapse owing to drug resistance. We aimed to identify potential serum biomarkers for predicting post-EGFR-TKI treatment relapse in patients with advanced-stage lung ADC. Methods: Among 27 patients, including 6 and 21 with early and late relapse, respectively, differentially expressed proteins between patients with early and late relapses were identified using liquid chromatography and tandem mass spectrometry and subsequently validated using Western blotting. Predictive ability was assessed using the receiver operating characteristic curve and area under the curve (AUC) analysis. The association between the clinical variables and treatment response was evaluated using the chi-square test. Results: The serum expression levels of the translocated promoter region (TPR), junction plakoglobin (JUP), and fibrinogen alpha chain (FGA) were significantly higher in patients with late rather than early relapse. The findings indicated that TPR and FGA exhibited good diagnostic performance, with AUCs of 0.946 (p = 0.002; 95% confidence interval [CI], 0.84–1.05) and 0.809 (p = 0.034; 95% CI, 0.65–0.97), respectively. Conclusions: Our results suggest that the TPR and FGA levels are potential predictors of post-EGFR-TKI treatment relapse. Full article

(This article belongs to the Special Issue Advances in Lung Cancer: From Bench to Bedside)

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15 pages, 485 KiB

Open AccessArticle

Omega-3 Polyunsaturated Fatty Acids (PUFAs) and Diabetic Peripheral Neuropathy: A Pre-Clinical Study Examining the Effect of Omega-3 PUFAs from Fish Oil, Krill Oil, Algae or Pharmaceutical-derived Ethyl Esters Using Type 2 Diabetic Rats

by Eric Davidson, Oleksandr Obrosov, Lawrence Coppey and Mark Yorek

Biomedicines 2025, 13(7), 1607; https://doi.org/10.3390/biomedicines13071607 - 30 Jun 2025

Abstract

Background and Objectives: We have previously reported that omega-3 polyunsaturated fatty acids (PUFAs) derived from fish oil (FO) is an effective treatment for type 1 and type 2 diabetes neural and vascular complications. As omega-3 PUFAs become more widely used as a nutritional [...] Read more.

Background and Objectives: We have previously reported that omega-3 polyunsaturated fatty acids (PUFAs) derived from fish oil (FO) is an effective treatment for type 1 and type 2 diabetes neural and vascular complications. As omega-3 PUFAs become more widely used as a nutritional and disease modifying supplement an important question to be addressed is what is the preferred source of omega-3 PUFAs? Methods: Using a type 2 diabetic rat model and early and late intervention protocols we examined the effect of dietary treatment with omega-3 PUFAs derived from menhaden (fish) oil (MO), krill oil (KO), algal oils consisting primarily of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) or combination of EPA + DHA, or pharmaceutical-derived ethyl esters of EPA, DHA or combination of EPA + DHA. Nerve related endpoints included motor and sensory nerve conduction velocity, heat sensitivity of the hind paw, intraepidermal nerve density, cornea nerve fiber length, and cornea sensitivity. Vascular reactivity to acetylcholine and calcitonin gene-related peptide by epineurial arterioles that provide blood to the sciatic nerve was also examined. Results: The dose of each omega-3 PUFA supplement increased the content of EPA, docosapentaenoic acid (DPA), and/or DHA in red blood cell membranes, serum and liver. Diabetes caused a significant decrease of 30–50% of neural function and fiber occupancy of the skin and cornea and vascular reactivity. Treatment with MO, KO or the combination of EPA + DHA provided through algal oil or ethyl esters provided significant improvement of each neural endpoint and vascular function. Algal oil or ethyl ester of EPA alone was the least effective with algal oil or ethyl ester of DHA alone providing benefit that approached combination therapies for some endpoints. Conclusions: We confirm that omega-3 PUFAs are an effective treatment for DPN and sources other than fish oil are similarly effective. Full article

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

22 pages, 6133 KiB

Open AccessArticle

Single-Cell Transcriptomic Analysis Unveils Key Regulators and Signaling Pathways in Lung Adenocarcinoma Progression

by Jialu Ma, Caleb McQuay, John Talburt, Amit K. Tiwari and Mary Qu Yang

Biomedicines 2025, 13(7), 1606; https://doi.org/10.3390/biomedicines13071606 - 30 Jun 2025

Abstract

Background: Lung adenocarcinoma (LUAD) remains a leading cause of cancer-related mortality despite advances in treatments, necessitating more effective therapeutic strategies. Single-cell RNA sequencing (scRNA-seq) technology has revolutionized our ability to dissect the cellular complexity of cancers, which is often obscured in conventional bulk [...] Read more.

Background: Lung adenocarcinoma (LUAD) remains a leading cause of cancer-related mortality despite advances in treatments, necessitating more effective therapeutic strategies. Single-cell RNA sequencing (scRNA-seq) technology has revolutionized our ability to dissect the cellular complexity of cancers, which is often obscured in conventional bulk transcriptomic experiments. Methods: In this study, we performed an integrative analysis of scRNA-seq data from multiple LUAD patient cohorts to investigate cell-type-specific transcriptomic changes across disease stages. Clustering, lineage trajectory analysis, and transcriptional regulatory network reconstruction were employed to identify stage-specific gene markers and their upstream regulators. Additionally, we constructed intercellular communication networks to evaluate signaling changes within the tumor microenvironment (TME) during LUAD progression. Results: Our analysis revealed that epithelial cells from stage IV tumors exhibited a distinct transcriptional profile compared to earlier stages, a separation not observed in immune or stromal cell populations. We identified a panel of gene markers that differentiated epithelial cells across disease stages and effectively stratified patients into subgroups with distinct survival outcomes and TME compositions. Regulatory network analysis uncovered key transcription factors, including ATF3, ATF4, HSF1, KLF4, and NFIC, as potential upstream regulators of these stage-specific genes. Moreover, cell–cell communication analysis revealed a significant increase in signaling originating from epithelial cells and a concomitant decrease in immune-derived signals in late-stage LUAD. We identified several signaling pathways enriched in stage-specific crosstalk, including Wnt, PTN, and PDGF pathways, which may play critical roles in LUAD progression. Conclusions: This study provides a comprehensive single-cell resolution map of LUAD progression, highlighting epithelial-driven regulatory programs and dynamic intercellular communication within the TME. Our findings uncover novel molecular markers and regulatory mechanisms with potential prognostic and therapeutic value for more precise treatment. Full article

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

16 pages, 1075 KiB

Open AccessArticle

Analysis of Vitamin D and VDR Expression in Women with Advanced Endometriosis: A Case–Control Study in Thailand

by Vitet Layanun, Woraluk Somboonporn, Pinya Aupongkaroon, Pilaiwan Kleebkaow, Nipon Chaisuriya and Naree Pluthikarmpae

Biomedicines 2025, 13(7), 1605; https://doi.org/10.3390/biomedicines13071605 - 30 Jun 2025

Abstract

Background: Vitamin D has anti-inflammatory and immunomodulatory properties that may influence the pathophysiology of endometriosis. This study investigated the association between vitamin D levels and endometriosis, and vitamin D receptor (VDR) expression in endometriotic tissue. Methods: A cross-sectional study was conducted involving 36 [...] Read more.

Background: Vitamin D has anti-inflammatory and immunomodulatory properties that may influence the pathophysiology of endometriosis. This study investigated the association between vitamin D levels and endometriosis, and vitamin D receptor (VDR) expression in endometriotic tissue. Methods: A cross-sectional study was conducted involving 36 patients with endometriosis and 72 healthy control women, matched for age and BMI. Serum 25-hydroxyvitamin D levels were measured and categorized into four statuses (normal, insufficiency, deficiency, and severe deficiency). Endometriotic tissue samples were examined for VDR expression using immunohistochemistry and qualitatively quantified using histo-scores (H-scores). Endometriosis severity was assessed using the revised criteria of the American Society for Reproductive Medicine (rASRM). Results: No statistically significant difference in vitamin D levels between the groups (20.45 vs. 21.10 ng/dL, p = 0.190) was observed, even after adjusting for residence, body sunscreen use, pregnancy, and contraceptive use. VDR expression exhibited significantly higher H-scores in endometriotic epithelial cells than in stromal cells (209.51 vs. 73.32; p < 0.001). Additionally, the VDR H-score in both cell compartments showed no significant difference according to vitamin D status. No statistically significant association was found between vitamin D levels, VDR expression, or disease severity. The odds of severe endometriosis were 2.17 (95% CI: 0.14–33.80) for vitamin D insufficiency and 4.33 (95% CI: 0.24–115.67) for deficiency compared with normal vitamin D. Conclusions: There was no statistically significant association between vitamin D levels and endometriosis and VDR. Full article

(This article belongs to the Special Issue Vitamin D: Latest Scientific Discoveries in Health and Disease)

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41 pages, 5389 KiB

Open AccessArticle

Diagnostic and Prognostic Roles of miR-155 and miR-3173 in Breast and Ovarian Cancer: Implications for Early Detection and Personalized Treatment

by Afaf Altrawy, Randa M. Talaat, Ghada M. Nasr, Eman A. E. Badr, Rebekka Arneth, Borros Arneth and Hussein Sabit

Biomedicines 2025, 13(7), 1604; https://doi.org/10.3390/biomedicines13071604 - 30 Jun 2025

Abstract

Objectives: The current study underscores the potential role of miRNAs, specifically miR-3173 and miR-155, as promising biomarkers for breast and ovarian cancers (BC and OC). The primary objective was to evaluate the expression levels of these miRNAs in cancer patients compared to healthy [...] Read more.

Objectives: The current study underscores the potential role of miRNAs, specifically miR-3173 and miR-155, as promising biomarkers for breast and ovarian cancers (BC and OC). The primary objective was to evaluate the expression levels of these miRNAs in cancer patients compared to healthy individuals, assess their diagnostic accuracy, and explore their associations with cancer progression and prognosis. Methods: This study involved 60 participants, comprising 30 patients diagnosed with primary BC and 30 patients with epithelial ovarian cancer (EOC). Tumor tissue samples were obtained from all patients for molecular analysis. For control comparisons, adjacent non-tumorous tissues from both groups were utilized. miR-3173 and miR-155 expression levels were measured using real-time PCR (qPCR). The diagnostic accuracy of both miRNAs was evaluated through receiver operating characteristic (ROC) curve analysis, calculating sensitivity and specificity for distinguishing cancer cases from healthy controls. Additionally, the association of miR-155 with metastasis was explored, and miR-3173’s correlation with poor progression-free survival in BC patients was assessed using Kaplan–Meier survival curve analysis. Results: Both miRNAs were found to be significantly upregulated in cancer patients compared to healthy individuals, with miR-155 exhibiting high sensitivity and specificity for distinguishing BC and OC cases. Notably, miR-155 is associated with metastasis, which aligns with previous research, suggesting its role as an oncogene in epithelial OC. Meanwhile, the elevated expression of miR-3173 correlates with poor progression-free survival in BC patients, marking it as a potential prognostic marker. However, these results highlight the complexity of miRNA expression in cancer progression, as miR-3173 showed varied associations with different types of cancer. Despite these challenges, the ROC curve analysis for both miRNAs is promising with high sensitivity and specificity for both BC and OC. Conclusion: The study findings are particularly significant in the context of early diagnosis and monitoring cancer progression, yet further investigations involving larger cohorts and diverse populations are needed to validate these results. Future studies should focus on expanding sample sizes, refining the understanding of miRNA roles in tumor progression, and exploring their potential as therapeutic targets. These advancements could significantly enhance personalized treatment strategies for breast and ovarian cancer, improving patient outcomes. Full article

(This article belongs to the Special Issue MicroRNAs as Mediators of Tumor Cell State Transitions, Receptor Remodeling, Drug Resistance, and Systemic Metastasis)

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19 pages, 1216 KiB

Open AccessArticle

Effect on Reduction in Inflammatory Fluid and Improvement of Cell Membrane/Skeletal Muscle by Far-Infrared Rays Emitted from Loess Bio-Balls During Sleep

by Yong Il Shin, Min Seok Kim, Yeong Ae Yang, Yun Jeong Lee, Gye Rok Jeon, Jae Ho Kim, Yeon Jin Choi, Woo Cheol Choi and Jae Hyung Kim

Biomedicines 2025, 13(7), 1603; https://doi.org/10.3390/biomedicines13071603 - 30 Jun 2025

Abstract

Background: Far infrared rays (FIR) can promote microcirculation of blood in capillaries and reduce inflammation and edema by improving lymphatic circulation. Although the short-term therapeutic use of FIR is increasingly common in clinical settings, its effects on inflammatory fluids during sleep are [...] Read more.

Background: Far infrared rays (FIR) can promote microcirculation of blood in capillaries and reduce inflammation and edema by improving lymphatic circulation. Although the short-term therapeutic use of FIR is increasingly common in clinical settings, its effects on inflammatory fluids during sleep are not yet well established. Methods: This was a small-scale exploratory study conducted on patients exhibiting early symptoms of edema or swelling, or participants who reported discomfort possibly due to such symptoms. Changes in impedance parameters related to inflammatory body fluids were measured in subjects (n = 55) lying lay on either a conventional electric mat (non-FIR) or a loess bio-ball mat (FIR) set at 40 °C for 30 min. To assess the effects of heat and FIR exposure during sleep, additional impedance measurements were taken in subjects (n = 60) who used either on an electric mat or a loess bio-ball mat set at 30 °C during sleep. Results: A total of 115 participants were included in four experimental conditions. In subjects exposed to conductive heat or FIR for 30 min while lying on an electric mat and a loess bio-ball mat set at 40 °C, only minimal changes were observed in impedance parameters and inflammatory fluid-related values. However, significant changes were seen in subjects (n = 30) who slept for 7 h on a loess bio-ball mat set at 30 °C. These changes are presumed to results from the deeper sleep and FIR emitted from the loess bio-balls. In contrast, no significant changes were observed in the group (n = 30) that used the electric mat at 30 °C under the same sleep conditions. Conclusions: Sleeping on a FIR-emitting loess bio-ball mat may stimulate biological tissues and lymphatic circulation, gradually reducing inflammatory fluid accumulation. This suggest potential benefits for improving the physiological condition and function of cell membranes and muscles. Full article

(This article belongs to the Section Biomedical Engineering and Materials)

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