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Biomedicines
Volume 12
Issue 11
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Biomedicines, Volume 12, Issue 11 (November 2024) – 233 articles

Cover Story (view full-size image): Age, C-reactive protein (CRP), fibrinogen, and absolute neutrophil count (ANC) are key predictors of chronic venous disease (CVD) progression. Specifically, elevated CRP and fibrinogen levels correlated strongly with increased CVD severity, particularly in patients with higher body mass index (BMI). BMI, while not an independent predictor, contributed indirectly to the disease severity through its association with these inflammatory markers. The logistic regression model incorporating age, BMI, CRP, fibrinogen, and ANC demonstrated a high predictive accuracy, highlighting the model’s reliability in stratifying patients at risk for severe CVD. This predictive model not only aids in identifying high-risk patients but also reinforces inflammation as a critical therapeutic target in CVD management. View this paper
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14 pages, 11240 KiB  
Article
Involvement of Lgals3/Galectin-3 in Choroidal Neovascularization and Subretinal Fibrosis Formation
by Di Wu, Ye Liu, Xiaogang Luo, Zhiqing Chen, Qiuli Fu and Ke Yao
Biomedicines 2024, 12(11), 2649; https://doi.org/10.3390/biomedicines12112649 - 20 Nov 2024
Viewed by 278
Abstract
Background: Lgals3/galectin-3 plays a pivotal role in many vascular diseases. However, the involvement of Lgals3/galectin-3 in eyes with neovascular age-related macular degeneration (nAMD) remains unknown. Methods: In the laser-induced CNV model, a whole mount retina stained with Isolectin B4 and [...] Read more.
Background: Lgals3/galectin-3 plays a pivotal role in many vascular diseases. However, the involvement of Lgals3/galectin-3 in eyes with neovascular age-related macular degeneration (nAMD) remains unknown. Methods: In the laser-induced CNV model, a whole mount retina stained with Isolectin B4 and collagen type I revealed the vascular bed and CNV-associated subretinal fibrosis on day 7 after laser treatment. Results: We show that the expression levels of Lgals3/galectin-3 were significantly increased in the RPE/choroidal complex of CNV mice. An intravitreal injection of Lgals3-siRNA significantly suppressed the area of CNV and subretinal fibrosis, together with Mcp-1 decline. The mixture of Lgals3-siRNA and Ranibizumab showed more efficiency than each drug used separately. Hypoxia induced Lgals3/galectin-3 production in ARPE-19 cells, which was reduced by the silencing hypoxia-inducible factor -1α (Hif-1a). Conclusions: Our data indicated that Lgals3/galectin-3 is involved in the pathogenesis of CNV and subretinal fibrosis, and Lgals3/galectin-3 could be a potential therapeutic target for nAMD. Full article
(This article belongs to the Section Cell Biology and Pathology)
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11 pages, 780 KiB  
Article
Mitral Valve Transcatheter Edge-to-Edge Repair (MV-TEER) in Patients with Secondary Mitral Regurgitation Improves Hemodynamics, Enhances Renal Function, and Optimizes Quality of Life in Patients with Advanced Renal Insufficiency
by Birgit Markus, Julian Kreutz, Giorgios Chatzis, Styliani Syntila, Jannis Kuchenbuch, Charlotte Mueller, Maryana Choukeir, Bernhard Schieffer and Nikolaos Patsalis
Biomedicines 2024, 12(11), 2648; https://doi.org/10.3390/biomedicines12112648 - 20 Nov 2024
Viewed by 364
Abstract
Background/Objectives: Secondary mitral regurgitation (MR) is a common valvular heart disease burdening the prognosis of patients with co-existing chronic heart failure. Transcatheter edge-to-edge mitral valve repair (MV-TEER) is a minimally invasive treatment option for high-risk patients. However, the effects of MV-TEER on expanded [...] Read more.
Background/Objectives: Secondary mitral regurgitation (MR) is a common valvular heart disease burdening the prognosis of patients with co-existing chronic heart failure. Transcatheter edge-to-edge mitral valve repair (MV-TEER) is a minimally invasive treatment option for high-risk patients. However, the effects of MV-TEER on expanded hemodynamics, tissue perfusion, and quality of life, particularly in patients with advanced renal failure, remain underexplored. Methods: This prospective, single-center study evaluated the impact of MV-TEER on hemodynamics, renal function, and quality of life in 45 patients with severe MR. Non-invasive bioimpedance monitoring with NICaS® was used to assess hemodynamics pre- and 3–5 days post-procedure. Quality of life was assessed using the EQ-5D-3L questionnaire before and 3 months post-procedure. For further analysis, patients were divided into subgroups based on the estimated baseline glomerular filtration rate (eGFR < 35 mL/min vs. eGFR ≥ 35 mL/min). Results: A significant reduction in systemic vascular resistance (SVR; p = 0.003) and an increase in eGFR (p = 0.03) were observed in the entire cohort after MV-TEER, indicating improved tissue perfusion. Notably, particularly patients with eGFR < 35 mL/min showed a significant increase in cardiac output (CO; p = 0.035), cardiac index (CI; p = 0.031), and eGFR (p = 0.018), as well as a reduction in SVR (p = 0.007). Consistent with these findings, quality of life significantly improved, with the EQ-5D-3L index and EQ-VAS score increasing from 0.44 to 0.66 (p < 0.001) and from 51.7% to 62.9% (p < 0.001). Full article
(This article belongs to the Special Issue Advanced Research in Cardiovascular and Hemodynamic Monitoring)
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15 pages, 1420 KiB  
Systematic Review
Update on the Biological and Clinical Relevance of Mast Cells in Chronic Rhinosinusitis with Nasal Polyps
by Luca Giovanni Locatello, Silvia Tonon, Vincenzo Mele, Simone Santini, Cesare Miani and Carlo Ennio Michele Pucillo
Biomedicines 2024, 12(11), 2647; https://doi.org/10.3390/biomedicines12112647 - 20 Nov 2024
Viewed by 234
Abstract
Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common inflammatory disorder whose complex immunopathogenesis has yet to be fully elucidated. Endotype-2 CRSwNP is the most common form of disease where eosinophils are the main drivers of inflammation. Traditional treatments for CRSwNP have centered [...] Read more.
Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common inflammatory disorder whose complex immunopathogenesis has yet to be fully elucidated. Endotype-2 CRSwNP is the most common form of disease where eosinophils are the main drivers of inflammation. Traditional treatments for CRSwNP have centered around intranasal or systemic corticosteroids and endoscopic sinus surgery (ESS). However, recent advancements in targeted therapies have introduced novel biological agents that specifically target key inflammatory mediators such as IL-4, IL-5, and IL-13. These biologics offer promising options for patients with CRSwNP, particularly those who do not respond adequately to conventional treatments. Nonetheless, some patients do not satisfactorily respond to these drugs because of an insufficient blockade of the inflammatory process. The mast cell (MC) is another important (and somehow neglected) actor in the pathogenesis of CRSwNP, and the latest clinical and translational evidence in this field has been reviewed in the present paper. Full article
(This article belongs to the Section Immunology and Immunotherapy)
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14 pages, 291 KiB  
Article
Untangling Depression in Schizophrenia: The Role of Disorganized and Obsessive-Compulsive Symptoms and the Duration of Untreated Psychosis
by Georgi Panov, Silvana Dyulgerova, Presyana Panova and Sonia Stefanova
Biomedicines 2024, 12(11), 2646; https://doi.org/10.3390/biomedicines12112646 - 20 Nov 2024
Viewed by 360
Abstract
Background: Schizophrenia is a complex disorder characterized by positive symptoms (e.g., hallucinations), negative symptoms (e.g., social withdrawal), and disorganized symptoms (e.g., thought disorder). Alongside these, cognitive and depressive symptoms often emerge, with depressive symptoms sometimes dominating the clinical picture. Understanding the factors that [...] Read more.
Background: Schizophrenia is a complex disorder characterized by positive symptoms (e.g., hallucinations), negative symptoms (e.g., social withdrawal), and disorganized symptoms (e.g., thought disorder). Alongside these, cognitive and depressive symptoms often emerge, with depressive symptoms sometimes dominating the clinical picture. Understanding the factors that influence the development of depressive symptoms in schizophrenia could clarify the dynamics between depressive and psychotic symptoms and guide clinical interventions. Methods: A total of 105 patients with schizophrenia (66 women, 39 men) were assessed using several clinical scales: PANSS, BPRS, DOCS, DES, HAM-D, and the Luria-Nebraska Neuropsychological Battery for cognitive evaluation. Statistical analyses, including correlation and regression, were conducted using SPSS to determine the significance of associations. Results: Disorganized and obsessive-compulsive symptoms were identified as primary factors associated with depressive symptoms in patients with schizophrenia. Conversely, a longer duration of untreated psychosis was linked to a lower severity of depressive symptoms, suggesting that early intervention may alter the depressive symptom trajectory. Conclusions: Here, we suggest a complex interaction between psychotic and depressive symptoms, possibly indicating a biological antagonism. The association of depressive symptoms with disorganized and obsessive-compulsive features may reflect an adaptive psychological response, attempting to stabilize amidst the disintegration of schizophrenia. These insights support a more integrated approach to treatment, addressing both psychotic and depressive symptoms to improve patient outcomes. Full article
(This article belongs to the Special Issue Dualistic Equilibrium in Neurotransmission and Beyond: Unraveling the Pathophysiology and Unlocking Novel Therapeutic Targets in Neuropsychiatric Disorders)
21 pages, 1622 KiB  
Review
Advancements in Autophagy Modulation for the Management of Oral Disease: A Focus on Drug Targets and Therapeutics
by Md Ataur Rahman, Mushfiq Hassan Shaikh, Rajat Das Gupta, Nazeeba Siddika, Muhammad Saad Shaikh, Muhammad Sohail Zafar, Bonglee Kim and Ehsanul Hoque Apu
Biomedicines 2024, 12(11), 2645; https://doi.org/10.3390/biomedicines12112645 - 19 Nov 2024
Viewed by 509
Abstract
Autophagy is an intrinsic breakdown system that recycles organelles and macromolecules, which influences metabolic pathways, differentiation, and thereby cell survival. Oral health is an essential component of integrated well-being, and it is critical for developing therapeutic interventions to understand the molecular mechanisms underlying [...] Read more.
Autophagy is an intrinsic breakdown system that recycles organelles and macromolecules, which influences metabolic pathways, differentiation, and thereby cell survival. Oral health is an essential component of integrated well-being, and it is critical for developing therapeutic interventions to understand the molecular mechanisms underlying the maintenance of oral homeostasis. However, because of the complex dynamic relationship between autophagy and oral health, associated treatment modalities have not yet been well elucidated. Determining how autophagy affects oral health at the molecular level may enhance the understanding of prevention and treatment of targeted oral diseases. At the molecular level, hard and soft oral tissues develop because of complex interactions between epithelial and mesenchymal cells. Aging contributes to the progression of various oral disorders including periodontitis, oral cancer, and periapical lesions during aging. Autophagy levels decrease with age, thus indicating a possible association between autophagy and oral disorders with aging. In this review, we critically review various aspects of autophagy and their significance in the context of various oral diseases including oral cancer, periapical lesions, periodontal conditions, and candidiasis. A better understanding of autophagy and its underlying mechanisms can guide us to develop new preventative and therapeutic strategies for the management of oral diseases. Full article
(This article belongs to the Section Cancer Biology and Oncology)
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17 pages, 6603 KiB  
Article
Multi-Algorithm-Integrated Tertiary Lymphoid Structure Gene Signature for Immune Landscape Characterization and Prognosis in Colorectal Cancer Patients
by Xianqiang Liu, Dingchang Li, Yue Zhang, Hao Liu, Peng Chen, Yingjie Zhao, Guanchao Sun, Wen Zhao and Guanglong Dong
Biomedicines 2024, 12(11), 2644; https://doi.org/10.3390/biomedicines12112644 - 19 Nov 2024
Viewed by 374
Abstract
Purpose: Colorectal cancer (CRC) is a common malignancy with a low survival rate as well as a low response rate to immunotherapy. This study aims to develop a risk model based on tertiary lymphoid structure (TLS)-associated gene signatures to enhance predictions of prognosis [...] Read more.
Purpose: Colorectal cancer (CRC) is a common malignancy with a low survival rate as well as a low response rate to immunotherapy. This study aims to develop a risk model based on tertiary lymphoid structure (TLS)-associated gene signatures to enhance predictions of prognosis and immunotherapy response. Methods: TLS-associated gene data were obtained from TCGA-CRC and GEO cohorts. A comprehensive analysis using univariate Cox regression identified TLS-associated genes with significant prognostic implications. Subsequently, multiple algorithms were employed to select the most influential genes, and a stepwise Cox regression model was constructed. The model’s predictive performance was validated using independent datasets (GSE39582, GSE17536, and GSE38832). To further investigate the immune microenvironment, immune cell infiltration in high-risk (HRG) and low-risk (LRG) groups was assessed using the CIBERSORT and ssGSEA algorithms. Additionally, we evaluated the model’s potential to predict immune checkpoint blockade therapy response using data from The Cancer Imaging Archive, the TIDE algorithm, and external immunotherapy cohorts (GSE35640, GSE78200, and PRJEB23709). Immunohistochemistry (IHC) was employed to characterize TLS presence and CCL2 gene expression. Results: A three-gene (CCL2, PDCD1, and ICOS) TLS-associated model was identified as strongly associated with prognosis and demonstrated predictive power for CRC patient outcomes and immunotherapy efficacy. Notably, patients in the low-risk group (LRG) had a higher overall survival rate as well as a higher re-response rate to immunotherapy compared to the high-risk group (HRG). Finally, IHC results confirmed significantly elevated CCL2 expression in the TLS regions. Conclusions: The multi-algorithm-integrated model demonstrated robust performance in predicting patient prognosis and immunotherapy response, offering a novel perspective for assessing immunotherapy efficacy. CCL2 may function as a TLS modulator and holds potential as a therapeutic target in CRC. Full article
(This article belongs to the Special Issue Morphomolecular Characterization of Neoplastic and Pre-neoplastic Lesions in Solid Tumors)
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19 pages, 8596 KiB  
Article
Molecular Basis for the Differential Function of HAVCR1 Mucin Variants
by Abdolrahim Abbasi, Maria Isabel Costafreda, Angela Ballesteros, Jerome Jacques, Cecilia Tami, Mohanraj Manangeeswaran, José M. Casasnovas and Gerardo Kaplan
Biomedicines 2024, 12(11), 2643; https://doi.org/10.3390/biomedicines12112643 - 19 Nov 2024
Viewed by 432
Abstract
Background/Objectives: The hepatitis A virus (HAV) cellular receptor 1 (HAVCR1) is a type I integral membrane glycoprotein discovered in monkeys and humans as a HAV receptor. HAVCR1 contains an N-terminal immunoglobulin-like variable domain (IgV) followed by a mucin-like domain (Muc), a transmembrane [...] Read more.
Background/Objectives: The hepatitis A virus (HAV) cellular receptor 1 (HAVCR1) is a type I integral membrane glycoprotein discovered in monkeys and humans as a HAV receptor. HAVCR1 contains an N-terminal immunoglobulin-like variable domain (IgV) followed by a mucin-like domain (Muc), a transmembrane domain, and a cytoplasmic tail with a canonical tyrosine kinase phosphorylation site. The IgV binds phosphatidylserine on apoptotic cells, extracellular vesicles, and enveloped viruses. Insertions/deletions at position 156 (156ins/del) of the Muc were associated in humans with susceptibility to atopic, autoimmune, and infectious diseases. However, the molecular basis for the differential function of the HAVCR1 variants is not understood. Methods: We used mutagenesis, apoptotic cell binding, and signal transduction analyses to study the role of the 156ins/del in the function of HAVCR1. Results: We found that the HAVCR1 variant without insertions at position 156 (156delPMTTTV, or short-HAVCR1) bound more apoptotic cells than that containing a six amino acid insertion (156insPMTTTV, or long-HAVCR1). Furthermore, short-HAVCR1 induced stronger cell signaling and phagocytosis than long-HAVCR1. Conclusions: Our data indicated that the 156ins/del determine how the IgV is presented at the cell surface and modulate HAVCR1 binding, signaling, and phagocytosis, suggesting that variant-specific targeting could be used as therapeutic interventions to treat immune and infectious diseases. Full article
(This article belongs to the Section Molecular Genetics and Genetic Diseases)
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10 pages, 764 KiB  
Article
The Influence of COVID-19 in Glycemic Control: Predictive Value of Inflammation and Metabolic Parameters
by Minodora Andor, Dana Emilia Man, Daciana Carmen Nistor, Valentina Buda and Simona Dragan
Biomedicines 2024, 12(11), 2642; https://doi.org/10.3390/biomedicines12112642 - 19 Nov 2024
Viewed by 353
Abstract
Background/Objectives: Predicting post-COVID-19 diabetes is crucial for enhancing patient care and public health. This study investigates the role of metabolic factors in predicting the glycemic outcomes in patients recovering from moderate to severe COVID-19. Methods: We conducted a retrospective analysis of 135 patients [...] Read more.
Background/Objectives: Predicting post-COVID-19 diabetes is crucial for enhancing patient care and public health. This study investigates the role of metabolic factors in predicting the glycemic outcomes in patients recovering from moderate to severe COVID-19. Methods: We conducted a retrospective analysis of 135 patients without pre-existing diabetes, selected from a cohort of 1980 individuals hospitalized between January 2020 and December 2022. Metabolic parameters, including blood glucose, Homeostasis Model Assessment of Insulin Resistance (HOMA-IR), Triglyceride/Glucose (TyG) index, and high-sensitivity C-reactive protein (hs-CRP), were assessed at discharge and followed up after 4 months (T4) and 12 months (T12). Results: Statistical analysis revealed significant correlations of initial glycemia, HOMA-IR, and hs-CRP with the subsequent glycemic levels at T4 and T12. Multiple regression analysis confirmed that initial glycemia, HOMA-IR, and hs-CRP were strong predictors of elevated glycemia, while the TyG index did not show a significant predictive value. Conventional diabetes risk factors, including body mass index (BMI) and lipid profiles, showed low predictive power for post-COVID-19 glycemia. Conclusions: This research highlights the critical role of metabolic and inflammatory pathways in managing glycemic control in COVID-19 patients. Markers like blood glucose, HOMA-IR, and hs-CRP are significant predictors of blood glucose levels, while the TyG index appears less helpful in this context. Early, targeted interventions based on these markers can improve patient outcomes and reduce the risk of post-COVID-19 complications like diabetes. Full article
(This article belongs to the Special Issue Connections Between Diabetes Mellitus, Other Metabolic and Endocrine Dysfunctions and Cardiovascular Pathologies)
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19 pages, 8593 KiB  
Article
A Metabolomic Approach to Unexplained Syncope
by Susanna Longo, Ilaria Cicalini, Damiana Pieragostino, Vincenzo De Laurenzi, Jacopo M. Legramante, Rossella Menghini, Stefano Rizza and Massimo Federici
Biomedicines 2024, 12(11), 2641; https://doi.org/10.3390/biomedicines12112641 - 19 Nov 2024
Viewed by 340
Abstract
Background: This study aims to identify a metabolomic signature that facilitates the classification of syncope and the categorization of the unexplained syncope (US) to aid in its management. Methods: We compared a control group (CTRL, n = 10) with a transient loss of [...] Read more.
Background: This study aims to identify a metabolomic signature that facilitates the classification of syncope and the categorization of the unexplained syncope (US) to aid in its management. Methods: We compared a control group (CTRL, n = 10) with a transient loss of consciousness (TLC) group divided into the OH group (n = 23) for orthostatic syncope, the NMS group (n = 26) for neuromediated syncope, the CS group (n = 9) for cardiological syncope, and the US group (n = 27) for US defined as syncope without a precise categorization after first- and second-level diagnostic approaches. Results: The CTRL and the TLC groups significantly differed in metabolic profile. A new logistic regression model has been developed to predict how the US will be clustered. Using differences in lysophosphatidylcholine with 22 carbon atom (C22:0-LPC) levels, 96% of the US belongs to the NMS and 4% to the CS subgroup. Differences in glutamine and lysine (GLN/LYS) levels clustered 95% of the US in the NMS and 5% in the CS subgroup. Conclusions: We hypothesize a possible role of C22:0 LPC and GLN/LYS in re-classifying US and differentiating it from cardiological syncope. Full article
(This article belongs to the Section Endocrinology and Metabolism Research)
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18 pages, 5974 KiB  
Article
Prognostic Significance and Immune Landscape of a Cuproptosis-Related LncRNA Signature in Ovarian Cancer
by Min Zhou, Jianming Tang, Guotao Huang and Li Hong
Biomedicines 2024, 12(11), 2640; https://doi.org/10.3390/biomedicines12112640 - 19 Nov 2024
Viewed by 304
Abstract
Background: Cuproptosis is a copper-induced mitochondrial cell death, and regulating cuproptosis is becoming a rising cancer treatment modality. Here, we attempted to establish a cuproptosis-associated lncRNAs (CRLs) signature (CRlncSig) to predict the survival, immune landscape, and treatment response in ovarian cancer (OC) patients. [...] Read more.
Background: Cuproptosis is a copper-induced mitochondrial cell death, and regulating cuproptosis is becoming a rising cancer treatment modality. Here, we attempted to establish a cuproptosis-associated lncRNAs (CRLs) signature (CRlncSig) to predict the survival, immune landscape, and treatment response in ovarian cancer (OC) patients. Methods: A series of statistical analyses were used to identify the key CRLs that are closely related to the prognosis, and a prognostic CRlncSig was constructed. The predictive accuracy of the CRlncSig was further validated in an independent Gene Expression Omnibus (GEO) set. Then, we compared the immune cell infiltration, immune checkpoints, tumor microenvironment (TME), tumor mutational burden (TMB), drug sensitivity, and efficacy of immunotherapy between the two subgroups. We further built a nomogram integrating the CRlncSig and different clinical traits to enhance the clinical application of the CRlncSig. Results: Nine hub CRLs, namely RGMB-AS1, TYMSOS, DANCR, LINC00702, LINC00240, LINC00996, DNM1P35, LINC00892, and TMEM254-AS1, were correlated with the overall survival (OS) of OC and a prognostic CRlncSig was established. The CRlncSig classified OC patients into two risk groups with strikingly different survival probabilities. The time-dependent ROC (tdROC) curves demonstrated good predictive ability in both the training cohort and an independent validation cohort. Multivariate analysis confirmed the independent predictive performance of the CRlncSig. We constructed a nomogram based on the CRlncSig, which can predict the prognosis of OC patients. The high-risk score was characterized by decreased immune cell infiltration and activation of stroma, while activation of immunity was observed in the low-risk subgroup. Moreover, patients in low-risk subgroups had more Immunophenoscore (IPS) and fewer immune escapes compared to high-risk subgroups. Finally, an immunotherapeutic cohort confirmed the value of the CRlncSig in predicting immunotherapy outcomes. Conclusions: The developed CRlncSig may be promising for the clinical prediction of OC patient outcomes and immunotherapeutic responses. Full article
(This article belongs to the Section Cancer Biology and Oncology)
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15 pages, 1757 KiB  
Article
Severe Malaria in Angola: The Clinical Profile and Disease Outcome Among Adults from a Low-Endemic Area
by Inês Morais, Soraia Rodrigues, Aida Mas, Serguei Escalon, Adalzira Borrego, Fatima Nogueira and Maria Lina Antunes
Biomedicines 2024, 12(11), 2639; https://doi.org/10.3390/biomedicines12112639 - 19 Nov 2024
Viewed by 324
Abstract
Background/Objectives: Severe malaria poses a significant public health concern in Angola, particularly among adults. This study assessed the clinical manifestations and outcomes of severe Plasmodium falciparum malaria in adult patients admitted to Hospital Central Dr. António Agostinho Neto of Lubango (HCL), Angola. Methods: [...] Read more.
Background/Objectives: Severe malaria poses a significant public health concern in Angola, particularly among adults. This study assessed the clinical manifestations and outcomes of severe Plasmodium falciparum malaria in adult patients admitted to Hospital Central Dr. António Agostinho Neto of Lubango (HCL), Angola. Methods: The study retrospectively reviewed medical records of patients over 14 years old admitted with severe malaria during the first quarter of 2021 and 2022, coinciding with the peak transmission season. The World Health Organization (WHO) criteria were used to clarify the disease severity. The cohort included 640 patients—167 in 2021 and 473 in 2022—distributed across the following departments: the Intensive Care Unit (ICU; n = 81), Medicine (MED; n = 458) and Infectiology (INF; n = 101). Results: The median age was 26 years and 59.4% were males. Renal impairment was the most frequent severe manifestation, affecting 37.4% of cases. The mortality rate across the study period was 7%, showing a notable decrease from 10.2% in 2021 to 5.9% in 2022. The higher mortality rate in 2021 may reflect the impact of the COVID-19 pandemic, which limited hospital access and delayed care, resulting in more critical cases being admitted at a later stage. In 2022, with reduced COVID-19 pressures, earlier access to treatment may have improved outcomes, contributing to the lower mortality rate. Conclusions: This study emphasizes the need to assess the clinical burden of severe malaria in low-endemic regions, where shifting patterns may signal emerging threats such as antimalarial drug resistance. Further research is essential to optimize control strategies and strengthen surveillance systems, reducing morbidity and mortality. Full article
(This article belongs to the Special Issue Emerging Viral Infectious Diseases: Immunology, Therapeutics and Prevention in Post Pandemic Era)
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14 pages, 271 KiB  
Article
Advanced Parameters of Myocardial Strain and Cardiac Biomarkers Indicate Subclinical Systolic Myocardial Dysfunction in Patients with Systemic Lupus Erythematous
by Nikolaos P. E. Kadoglou, Alexandriani Dimopoulou, Ioannis Korakianitis and Konstantinos Parperis
Biomedicines 2024, 12(11), 2638; https://doi.org/10.3390/biomedicines12112638 - 19 Nov 2024
Viewed by 267
Abstract
Background: Systemic lupus erythematosus (SLE) is characterized by inflammation and cardiovascular complications. Our study aimed to investigate subclinical and early indicators of systolic myocardial dysfunction in SLE patients using advanced echocardiographic methods and biomarkers. Methods: In this cross-sectional study, we enrolled [...] Read more.
Background: Systemic lupus erythematosus (SLE) is characterized by inflammation and cardiovascular complications. Our study aimed to investigate subclinical and early indicators of systolic myocardial dysfunction in SLE patients using advanced echocardiographic methods and biomarkers. Methods: In this cross-sectional study, we enrolled 102 SLE patients without known cardiac impairment and 51 healthy controls. Demographics, disease characteristics, laboratory results, disease activity (SLEDAI), and organ damage (SDI) indices were recorded. Left ventricular global longitudinal strain (GLS) and myocardial work indices were assessed by utilizing speckle tracking echocardiography. In addition, high-sensitivity C-reactive protein (hsCRP), high-sensitivity troponin (hsTn), and N-terminal-pro B-type natriuretic peptide (NT-proBNP) levels were measured in blood samples. Results: In comparison with controls, SLE patients had significantly higher GLS (−19.94 ± 2.71% vs. −21.15 ± 1.55%, p < 0.001) and global wasted work (GWW) (94 ± 71 mmHg% vs. 71 ± 49 mmHg%, p = 0.025). Notably, NT-proBNP and hsTn were threefold and twofold higher in the SLE group compared with the control group, respectively (p < 0.001). Within the SLE cohort, in patients with at least moderate disease activity (SLEDAI ≥ 4), both biomarkers were significantly more elevated than those with low disease activity (SLEDAI < 4). Notably, hsTn levels remained within the normal range. Conclusions: Advanced echocardiographic parameters combined with specific biomarkers have a promising role in detecting systolic dysfunction in SLE patients, potentially enabling timely interventions to mitigate cardiovascular risk Full article
(This article belongs to the Special Issue Identification and Validation of New Biomarkers to Help the Creation of Clinical Diagnostics in Autoimmune and Cancer Diseases)
23 pages, 1336 KiB  
Article
Changes in IL-6, IL-12, IL-5, IL-10 and TGF-β1 Concentration in Patients with Treatment-Resistant Schizophrenia (TRS) Following Electroconvulsive Therapy (ECT)—A Pilot Study
by Anna Maria Szota, Izabela Radajewska, Małgorzata Ćwiklińska-Jurkowska, Kinga Lis, Przemysław Grudzka and Wiktor Dróżdż
Biomedicines 2024, 12(11), 2637; https://doi.org/10.3390/biomedicines12112637 - 19 Nov 2024
Viewed by 338
Abstract
Background/Objectives: Treatment-resistant schizophrenia (TRS) may be considered as a neuro-immune disorder. Electroconvulsive therapy (ECT) remains an important therapeutic option for patients with TRS, however, its impact on cytokine profile is barely investigated. Therefore, this study attempts to establish associations between serum cytokines IL-6, [...] Read more.
Background/Objectives: Treatment-resistant schizophrenia (TRS) may be considered as a neuro-immune disorder. Electroconvulsive therapy (ECT) remains an important therapeutic option for patients with TRS, however, its impact on cytokine profile is barely investigated. Therefore, this study attempts to establish associations between serum cytokines IL-6, IL-12, IL-5, IL-10 and TGF-β1 changes (pre- and post-ECT) and the effectiveness of ECT in TRS patients. The second aim is to search for correlations between serum concentrations of the above specified cytokines and psychometric assessments of clinical schizophrenia symptoms. Methods: The cytokine concentrations were measured in eight TRS patients on psychopharmacological treatment prior to and following ECT and in 13 control subjects. Psychopathology assessment was based on the Positive and Negative Syndrome Scale (PANSS). Results: Prior to ECT, IL-10 concentration was significantly higher in TRS patients, while IL-5 was decreased in comparison to the controls. A significant concentration decrease in the pro-inflammatory cytokines IL-6 (p = 0.012), IL-12 (p = 0.049) and anti-inflammatory IL-10 (p = 0.012) post-ECT vs. pre-ECT was observed, whereas concentrations of IL-5 and TGF-β1 did not significantly change. Also, a significant decrease in schizophrenia symptoms measured by the PANSS post-ECT was found. Furthermore, the pattern of correlations between PANSS scores and cytokine concentrations was different when comparing levels pre- and post-ECT. Additionally, correlations between changes in PANSS scores and cytokine concentrations were found. Conclusions: These results may indicate the probable impact of electroconvulsive therapy on the balance between pro- and anti-inflammatory cytokines, which may correspond to a neurobiological therapeutic effect of ECT in TRS patients. Full article
(This article belongs to the Special Issue Advanced in Schizophrenia Research and Treatment)
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16 pages, 690 KiB  
Review
Disease Modifying Monoclonal Antibodies and Symptomatic Pharmacological Treatment for Alzheimer’s Disease
by Xiaoming Qi, Damir Nizamutdinov, Song Stephen Yi, Erxi Wu and Jason H. Huang
Biomedicines 2024, 12(11), 2636; https://doi.org/10.3390/biomedicines12112636 - 19 Nov 2024
Viewed by 382
Abstract
Alzheimer’s Disease (AD) is an irreversible, progressive syndrome characterized by neurocognitive impairment. Two neuropathological features seen in AD are extracellular amyloid plaques consisting of amyloid beta1-40 and 1-42, and intracellular neurofibrillary tangles (NFTs). For decades, neuroscience research has heavily focused on seeking to [...] Read more.
Alzheimer’s Disease (AD) is an irreversible, progressive syndrome characterized by neurocognitive impairment. Two neuropathological features seen in AD are extracellular amyloid plaques consisting of amyloid beta1-40 and 1-42, and intracellular neurofibrillary tangles (NFTs). For decades, neuroscience research has heavily focused on seeking to understand the primary mechanism of AD and searching for pharmacological approaches for the treatment of dementia. Three monoclonal antibodies that act against amyloid beta—aducanumab, lecanemab, and donanemab—have been approved by the Food and Drug Administration (FDA) for the treatment of mild cognitive impairment and mild AD, in addition to medications for cognitive symptom management such as acetylcholinesterase inhibitors and the N-methyl-D-aspartate (NMDA) antagonist. Further trials should focus on the combination of therapies targeting amyloid plaques and tau pathology. Full article
(This article belongs to the Special Issue Alzheimer's Disease—115 Years after Its Discovery 2.0)
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10 pages, 1346 KiB  
Article
Efficacy of High-Definition Transcranial Alternating Current Stimulation (HD-tACS) at the M1 Hotspot Versus C3 Site in Modulating Corticospinal Tract Excitability
by Hao Meng, Michael Houston, Nicholas Dias, Chen Guo, Gerard Francisco, Yingchun Zhang and Sheng Li
Biomedicines 2024, 12(11), 2635; https://doi.org/10.3390/biomedicines12112635 - 19 Nov 2024
Viewed by 363
Abstract
Previous studies have shown that beta-band transcranial alternating current stimulation (tACS) applied at the M1 hotspot can modulate corticospinal excitability. However, it remains controversial whether tACS can influence motor unit activities at the spinal cord level. This study aims to compare the efficacy [...] Read more.
Previous studies have shown that beta-band transcranial alternating current stimulation (tACS) applied at the M1 hotspot can modulate corticospinal excitability. However, it remains controversial whether tACS can influence motor unit activities at the spinal cord level. This study aims to compare the efficacy of applying tACS over the hotspot versus the conventional C3 site on motor unit activities and subsequent behavioral changes. This study used a randomized crossover trial design, where fifteen healthy participants performed a paced ball-squeezing exercise while receiving high-definition tACS (HD-tACS) at 21 Hz and 2 mA for 20 min. HD-tACS targeted either the flexor digitorum superficialis (FDS) hotspot or the C3 site, with the order of stimulation randomized for each participant and a 1-week washout period between sessions. Motor unit activities were recorded from the FDS. HD-tACS intervention significantly reduced the variability of motor unit firing rates and increased force variability during isometric force production. The significant modulation effects were seen only when the intervention was applied at the hotspot, but not at the C3 site. Our findings demonstrate that HD-tACS significantly modulates motor unit activities and force variability. The results indicate that cortical-level entrainment by tACS can lead to the modulation of spinal motor neuron activities. Additionally, this study provides further evidence that the C3 site may not be the optimal target for tACS intervention for hand muscles, highlighting the need for personalized neuromodulation strategies. Full article
(This article belongs to the Collection Feature Papers in Neuromodulation and Brain Stimulation)
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13 pages, 680 KiB  
Article
Types of Injuries and the Severity of Shoulder Dysfunction Associated with Diabetes Mellitus in Patients with Functional Impairment: A Case–Control Study
by Mercedes Fuentes-Murguia, Karla B. Carrazco-Peña, Osiris G. Delgado-Enciso, Joel Castellanos-Gomez, Gustavo A. Hernandez-Fuentes, Fabian Rojas-Larios, Carmen A. Sanchez-Ramirez, Margarita L. Martinez-Fierro, Iram P. Rodriguez-Sanchez, José Guzmán-Esquivel, Idalia Garza-Veloz, José E. Del-Río-Valdivia, Jorge E. Plata-Florenzano and Iván Delgado-Enciso
Biomedicines 2024, 12(11), 2634; https://doi.org/10.3390/biomedicines12112634 - 18 Nov 2024
Viewed by 484
Abstract
Background/Objectives: Patients with diabetes have been reported to experience a higher prevalence of shoulder disorders compared to those without diabetes or with other medical conditions. However, the specific types of shoulder injuries and the extent of functional impairment associated with diabetes mellitus remain [...] Read more.
Background/Objectives: Patients with diabetes have been reported to experience a higher prevalence of shoulder disorders compared to those without diabetes or with other medical conditions. However, the specific types of shoulder injuries and the extent of functional impairment associated with diabetes mellitus remain unclear. This study aimed to assess the association between diabetes and specific shoulder injuries, as well as the degree of functional impairment in affected patients. Methods: A case–control study was conducted involving 136 patients with shoulder functional impairment (UCLA Shoulder Scale ≤ 27). The study included 38 patients with diabetes and 98 non-diabetic controls. Shoulder injuries were diagnosed using ultrasonography, focusing on the supraspinatus tendon, long head of the biceps tendon, subscapularis tendon, and the presence of adhesive capsulitis or rotator cuff tears. Results: Diabetic patients had significantly higher rates of poor shoulder function compared to non-diabetic controls (89.47% vs. 63.26%, adjusted OR [adOR] 5.22, 95% CI 1.57–17.32, p = 0.007). While both groups had high rates of supraspinatus and long head of the biceps tendon injuries (~80%), no significant differences were found between them (p > 0.300). However, diabetic patients were more than three times as likely to have subscapularis tendon injuries (adOR 3.15, 95% CI 1.26–7.90, p = 0.014) and massive rotator cuff tears (adOR 3.76, 95% CI 1.16–12.15, p = 0.027). Additionally, diabetes was associated with a fourfold increased risk of adhesive capsulitis (adOR 4.16, 95% CI 1.20–14.47, p = 0.025). Conclusions: Diabetes mellitus is linked to greater functional and structural deterioration of the shoulder, highlighting the importance of considering diabetes as a risk factor for specific shoulder injuries. Early diagnosis and treatment may improve outcomes for diabetic patients with shoulder disorders. Full article
(This article belongs to the Special Issue Molecular Research on Osteoarthritis and Osteoporosis)
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11 pages, 1081 KiB  
Article
Selective Serotonin Reuptake Inhibitors for Cessation of Betel Quid Use in Patients with Major Depressive Disorder in Taiwan
by Chung-Chieh Hung, Hung-Pin Tu and Chia-Min Chung
Biomedicines 2024, 12(11), 2633; https://doi.org/10.3390/biomedicines12112633 - 18 Nov 2024
Viewed by 370
Abstract
Background/Objectives: Major depressive disorder (MDD) frequently co-occurs with substance use disorders such as alcohol and nicotine use disorders. Comorbid substance use disorders worsen the clinical symptoms of MDD and exacerbate addictive behaviors and presentations. However, the relationship between MDD and betel quid [...] Read more.
Background/Objectives: Major depressive disorder (MDD) frequently co-occurs with substance use disorders such as alcohol and nicotine use disorders. Comorbid substance use disorders worsen the clinical symptoms of MDD and exacerbate addictive behaviors and presentations. However, the relationship between MDD and betel quid use disorder (BUD) in Taiwan has not been extensively investigated. Methods: We performed this cross-sectional study investigated associations between betel quid use, BUD, and MDD specifically in the Taiwanese population. Long-term betel quid use is a major public health concern, contributing significantly to the high incidence of oral cancers, which rank fifth among the top ten most common cancers in Taiwan. Results: Among patients with MDD, the current BUD prevalence rate was 7.32%, and the lifetime BUD prevalence rate was 15.45%. Patients with comorbid BUD were more likely to have severe alcohol and nicotine dependence disorders and required longer antidepressant treatment. Conclusions: Notably, 16.98% of patients with comorbid BUD who received selective serotonin reuptake inhibitor treatment achieved abstinence. BUD has a detrimental effect on health outcomes in patients with MDD, and selective serotonin reuptake inhibitor treatment may be required to be prolonged for betel quid abstinence therapy to be effective. Additional studies should investigate medication therapies for betel quid addiction disorders. Full article
(This article belongs to the Section Neurobiology and Clinical Neuroscience)
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14 pages, 3475 KiB  
Article
Gallic Acid Induces HeLa Cell Lines Apoptosis via the P53/Bax Signaling Pathway
by Umut Sarı, Fuat Zaman, İlhan Özdemir, Şamil Öztürk and Mehmet Cudi Tuncer
Biomedicines 2024, 12(11), 2632; https://doi.org/10.3390/biomedicines12112632 - 18 Nov 2024
Viewed by 401
Abstract
Background: Cervical cancer is a type of cancer that originates from the endometrium and is more common in developed countries and its incidence is increasing day by day in developing countries. The most commonly prescribed chemotherapeutic drugs limit their use due to serious [...] Read more.
Background: Cervical cancer is a type of cancer that originates from the endometrium and is more common in developed countries and its incidence is increasing day by day in developing countries. The most commonly prescribed chemotherapeutic drugs limit their use due to serious side effects and the development of drug resistance. For this reason, interest in new active ingredients obtained from natural products is increasing. This study aimed to reveal the apoptotic and antiproliferative effects of gallic acid and doxorubicin combination therapy against the HeLa cell line. Methods: We investigated the anti-cancer effects of doxorubicin and gallic acid in the human HeLa cervical cell line by using the MTT test, Nucblue staining for the identification of apoptotic cells due to nuclear condensation using fluorescent substance, and apoptotic markers P53 and Bax for the RT-PCR test. Results: The highest cytotoxic effect obtained in the study, the highest increase in apoptotic induction, and a significant difference in P53/Bax levels were seen in the gallic acid/doxorubicin combination. Additionally, it was determined that gallic acid exhibited an effective cytotoxic effect on HeLa and HaCat cells within 48 and 72 h of application. Conclusions: The obtained findings show that the gallic acid/doxorubicin combination applied to HeLa cells may be an alternative treatment against both the cytotoxic effect size and the side effects of the chemotherapy agent. Full article
(This article belongs to the Collection Feature Papers in Cell Biology and Pathology)
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39 pages, 1421 KiB  
Review
The Role of HDAC6 in Glioblastoma Multiforme: A New Avenue to Therapeutic Interventions?
by Francesco Spallotta and Barbara Illi
Biomedicines 2024, 12(11), 2631; https://doi.org/10.3390/biomedicines12112631 - 17 Nov 2024
Viewed by 508
Abstract
Despite the great advances in basic research results, glioblastoma multiforme (GBM) still remains an incurable tumour. To date, a GBM diagnosis is a death sentence within 15–18 months, due to the high recurrence rate and resistance to conventional radio- and chemotherapy approaches. The [...] Read more.
Despite the great advances in basic research results, glioblastoma multiforme (GBM) still remains an incurable tumour. To date, a GBM diagnosis is a death sentence within 15–18 months, due to the high recurrence rate and resistance to conventional radio- and chemotherapy approaches. The effort the scientific community is lavishing on the never-ending battle against GBM is reflected by the huge number of clinical trials launched, about 2003 on 10 September 2024. However, we are still far from both an in-depth comprehension of the biological and molecular processes leading to GBM onset and progression and, importantly, a cure. GBM is provided with high intratumoral heterogeneity, immunosuppressive capacity, and infiltrative ability due to neoangiogenesis. These features impact both tumour aggressiveness and therapeutic vulnerability, which is further limited by the presence in the tumour core of niches of glioblastoma stem cells (GSCs) that are responsible for the relapse of this brain neoplasm. Epigenetic alterations may both drive and develop along GBM progression and also rely on changes in the expression of the genes encoding histone-modifying enzymes, including histone deacetylases (HDACs). Among them, HDAC6—a cytoplasmic HDAC—has recently gained attention because of its role in modulating several biological aspects of GBM, including DNA repair ability, massive growth, radio- and chemoresistance, and de-differentiation through primary cilia disruption. In this review article, the available information related to HDAC6 function in GBM will be presented, with the aim of proposing its inhibition as a valuable therapeutic route for this deadly brain tumour. Full article
(This article belongs to the Special Issue Diagnosis, Pathogenesis and Treatment of CNS Tumors)
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17 pages, 2832 KiB  
Systematic Review
Digestive Amyloidosis Trends: Clinical, Pathological, and Imaging Characteristics
by Sandica Bucurica, Andreea-Simona Nancoff, Miruna Valeria Moraru, Ana Bucurica, Calin Socol, Daniel-Vasile Balaban, Mihaela Raluca Mititelu, Ionela Maniu, Florentina Ionita-Radu and Mariana Jinga
Biomedicines 2024, 12(11), 2630; https://doi.org/10.3390/biomedicines12112630 - 17 Nov 2024
Viewed by 576
Abstract
Amyloidosis is a group of diseases characterized by the extracellular deposition of abnormally folded, insoluble proteins that lead to organ dysfunction. While it commonly affects the cardiovascular system, gastrointestinal (GI) tract involvement is undetermined. Recent research has focused on understanding the pathophysiology, diagnostic [...] Read more.
Amyloidosis is a group of diseases characterized by the extracellular deposition of abnormally folded, insoluble proteins that lead to organ dysfunction. While it commonly affects the cardiovascular system, gastrointestinal (GI) tract involvement is undetermined. Recent research has focused on understanding the pathophysiology, diagnostic challenges, and therapeutic approaches to GI amyloidosis, particularly in systemic amyloid light-chain (AL) and amyloid A (AA) forms. GI manifestations can include motility disorders, bleeding, and, in severe cases, bowel obstruction. This review highlights the importance of the early recognition of digestive symptoms and associated imagistic findings in GI amyloidosis by analyzing the research that included clinical, pathological, and endoscopic approaches to amyloidosis. A systematic search of the PubMed and Scopus databases identified 19 relevant studies. Our findings showed that amyloid deposits commonly affect the entire GI tract, with AL amyloidosis being the most predominant form. Endoscopic evaluations and biopsy remain key diagnostic tools, with Congo Red staining and mass spectrometry being used to confirm amyloid type. Although progress has been made in diagnosis, the absence of targeted therapies and the indistinct nature of GI symptoms continue to be challenging. Full article
(This article belongs to the Special Issue Pancreatic, Liver, Biliary Tract and Intestinal Diseases: Pathogenesis, Diagnostics and Therapy)
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19 pages, 5471 KiB  
Article
Chamomile Tincture and Lidocaine Hydrochloride Gel Ameliorates Periodontitis: A Preclinical Study
by Jiahui Sun, Huiyi Wang, Junhong Xiao, Qiudong Yang, Heyu Liu, Zhengkun Yang, Yuqi Liu, Xin Huang, Liu Yang, Li Ma and Zhengguo Cao
Biomedicines 2024, 12(11), 2629; https://doi.org/10.3390/biomedicines12112629 - 17 Nov 2024
Viewed by 378
Abstract
Background/Objectives: Periodontitis is a common oral disease marked by gingival inflammation and alveolar bone loss. This study evaluated the efficacy of chamomile tincture and lidocaine hydrochloride (CLH) gel in mitigating periodontal inflammation and bone loss and uncovered the molecular mechanisms involved, both [...] Read more.
Background/Objectives: Periodontitis is a common oral disease marked by gingival inflammation and alveolar bone loss. This study evaluated the efficacy of chamomile tincture and lidocaine hydrochloride (CLH) gel in mitigating periodontal inflammation and bone loss and uncovered the molecular mechanisms involved, both in vitro and in vivo. Methods: A periodontitis model was induced in Sprague Dawley rats by ligating the mandibular first molars. Sixty rats were divided into four groups: control (C), periodontitis (PD), periodontitis + CLH gel once daily (G1), and periodontitis + CLH gel thrice daily (G3). Clinical, micro-computed tomography (micro-CT), biological, and histological evaluations were performed, focusing on osteoclastogenesis, osteogenesis, and inflammatory cytokine production. The effect of CLH gel on inflammatory responses in RAW264.7 cells was also assessed through co-culture assays under Porphyromonas gingivalis (P. gingivalis) infection, with RNA-sequencing, qPCR, and Western blot analyses to explore underlying mechanisms. Results: CLH gel significantly reduced gingival and systemic inflammation and mitigated bone loss by enhancing the bone volume to tissue volume ratio and trabecular thickness via the RANKL/OPG axis in rats. The G3 group showed marked reductions in osteoclasts and increases in osterix-positive cells compared to other groups. In vitro, CLH gel reduced the inflammatory phenotype of macrophages in the periodontitis microenvironment by modulating Type II interferon (IFN-γ) networks. Conclusions: CLH gel reduced inflammation and bone loss in rat periodontitis, promoting osteogenesis and inhibiting osteoclastogenesis. It also suppressed macrophage inflammation via Type II interferon networks under P. gingivalis stimulation. These findings suggest that CLH gel has potential as an adjunctive therapy for periodontitis. Full article
(This article belongs to the Section Drug Discovery, Development and Delivery)
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21 pages, 777 KiB  
Article
Antithyroglobulin and Antiperoxidase Antibodies Can Negatively Influence Pregnancy Outcomes by Disturbing the Placentation Process and Triggering an Imbalance in Placental Angiogenic Factors
by Kamila Tańska, Piotr Glinicki, Beata Rebizant, Piotr Dudek, Wojciech Zgliczyński and Małgorzata Gietka-Czernel
Biomedicines 2024, 12(11), 2628; https://doi.org/10.3390/biomedicines12112628 - 17 Nov 2024
Viewed by 275
Abstract
Background/Objectives: Thyroid autoimmunity (TAI) affects about 15% of women of reproductive age and can negatively affect pregnancy outcomes. One possible mechanism for pregnancy complications can be attributed to a disturbed process of placentation caused by thyroid antibodies. To test this hypothesis, placental [...] Read more.
Background/Objectives: Thyroid autoimmunity (TAI) affects about 15% of women of reproductive age and can negatively affect pregnancy outcomes. One possible mechanism for pregnancy complications can be attributed to a disturbed process of placentation caused by thyroid antibodies. To test this hypothesis, placental hormones and angiogenic factors in pregnant women with TAI were evaluated. Methods: Fifty-eight hypothyroid women positive for TPOAb/TgAb, thirty-three hypothyroid women negative for TPOAb/TgAb, and thirty-nine healthy controls were enrolled in this study. Maternal thyroid function tests were established every month throughout pregnancy, and angiogenic placental factors, pro-angiogenic placental growth factor (PlGF); two anti-angiogenic factors, soluble vascular endothelial growth factor receptor 1 (sFlt-1) and soluble endoglin (sEng); and placental hormones, estradiol, progesterone, and hCG, were determined during each trimester. Results: Obstetrical and neonatal outcomes did not differ between the groups. However, several detrimental effects of thyroid antibodies were observed. These included a positive correlation between TgAb and the sEng/PlGF ratio in the first trimester and positive correlations between TPOAb and sFlt-1 and between TgAb and the sFlt-1/PlGF ratio in the third trimester. TgAbs in the first trimester was a risk factor for gestational hypertension and preeclampsia. Conclusions: Our study indicates that TPOAbs and TgAbs can exert a direct harmful effect on placentation, leading to disturbances in the production of placental angiogenic factors and, consequently, to an increased risk of gestational hypertension and preeclampsia. Full article
(This article belongs to the Special Issue Thyroid Disorders: Current Status and Future Prospects)
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38 pages, 21275 KiB  
Review
Pancreatic Morphology, Immunology, and the Pathogenesis of Acute Pancreatitis
by Tudorel Mihoc, Silviu Constantin Latcu, Cosmin-Ciprian Secasan, Vlad Dema, Alin Adrian Cumpanas, Mircea Selaru, Catalin Alexandru Pirvu, Andrei Paul Valceanu, Flavia Zara, Cristina-Stefania Dumitru, Dorin Novacescu and Stelian Pantea
Biomedicines 2024, 12(11), 2627; https://doi.org/10.3390/biomedicines12112627 - 17 Nov 2024
Viewed by 442
Abstract
Acute pancreatitis is a complex inflammatory disorder with significant morbidity and mortality. This review aims to integrate the current knowledge of pancreatic morphology and immunology with the pathogenesis of acute pancreatitis, providing a comprehensive understanding of this critical condition. We conducted an extensive [...] Read more.
Acute pancreatitis is a complex inflammatory disorder with significant morbidity and mortality. This review aims to integrate the current knowledge of pancreatic morphology and immunology with the pathogenesis of acute pancreatitis, providing a comprehensive understanding of this critical condition. We conducted an extensive literature review, synthesizing data from recent studies and authoritative sources on pancreatic anatomy, histology, immunology, and the pathophysiology of acute pancreatitis. We also incorporated epidemiological data, clinical features, diagnostic criteria, and prognostic factors. The pancreas exhibits a complex morphology with intricate interactions between its exocrine and endocrine components. Its unique immunological landscape plays a crucial role in maintaining homeostasis and orchestrating responses to pathological conditions. In acute pancreatitis, the disruption of intracellular calcium signaling leads to premature enzyme activation, triggering a cascade of events including mitochondrial dysfunction, ATP depletion, and the release of proinflammatory mediators. This process can escalate from localized inflammation to systemic complications. The interplay between pancreatic morphology, immune responses, and pathophysiological mechanisms contributes to the varied clinical presentations and outcomes observed in acute pancreatitis. Understanding the intricate relationships between pancreatic morphology, immunology, and the pathogenesis of acute pancreatitis is crucial for developing more effective diagnostic and therapeutic strategies. This integrated approach provides new insights into the complex nature of acute pancreatitis and may guide future research directions in pancreatic disorders. Full article
(This article belongs to the Special Issue Acute Pancreatitis: Biology, Diagnosis and Therapy)
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12 pages, 2408 KiB  
Article
Tumor Suppressor miR-27a-5p and Its Significance for Breast Cancer
by Paola Parrella, Raffaela Barbano, Katharina Jonas, Andrea Fontana, Serena Barile, Michelina Rendina, Antonio lo Mele, Giuseppina Prencipe, Luigi Ciuffreda, Maria Grazia Morritti, Vanna Maria Valori, Paolo Graziano, Evaristo Maiello, Massimiliano Copetti, Martin Pichler and Barbara Pasculli
Biomedicines 2024, 12(11), 2625; https://doi.org/10.3390/biomedicines12112625 - 17 Nov 2024
Viewed by 427
Abstract
Background: MicroRNAs are well established as master regulators of carcinogenesis and potential biomarkers in breast cancer (BC). In a preliminary effort, we found miR-27a-5p to be significantly downregulated in experimentally derived mammospheres and BC patients from The Cancer Genome Atlas Breast Invasive Carcinoma [...] Read more.
Background: MicroRNAs are well established as master regulators of carcinogenesis and potential biomarkers in breast cancer (BC). In a preliminary effort, we found miR-27a-5p to be significantly downregulated in experimentally derived mammospheres and BC patients from The Cancer Genome Atlas Breast Invasive Carcinoma (TCGA-BRCA) dataset. Objectives. Herein, we sought to investigate the putative involvement of miR-27a-5p in promoting a migratory phenotype of breast cancer cells, and establish whether miR-27a-5p is associated with patient clinicopathological characteristics. Methods: miR-27a-5p capability of inducing a metastasis-prone cell phenotype was analyzed in SUM159 and MDA-MB-231, both representing the triple negative BC subtype. miR-27a-5p expression profile was carried out in a cohort of 232 BC patients and normal breast tissues (NBTs) by RT-qPCR. Results: Transient miR-27a-5p inhibition did not affect cell proliferation but led to a significant increase of cell migration in knocked-down compared to control cells. Following quantification in the patient cohort, miR-27a-5p was found higher in NBTs (Median 2.28, IQR 1.50–5.40) and pre-invasive breast lesions (Median 3.32, IQR 1.68–4.32) compared to tumors. In particular, miR-27a-5p was less expressed in patients with synchronous (Median 1.03, IQR 0.83–1.58) or metachronous (Median 1.83, IQR 1.29–3.17) metastases than in patients free from metastases after a 5-year follow-up (Median 2.17, IQR 1.19–3.64), suggesting that miR-27a-5p expression is negatively correlated with breast pathology evolution (R = −0.13, p = 0.038). However, time-to-event analysis did not highlight significant associations with patient outcome in either our internal cohort or TCGA-BRCA dataset. Conclusions: Our study suggests a potential role of miR-27a-5p as tumor suppressor miRNA in breast cancer. Further investigations may help define its biomarker potential in each breast cancer subtype, and identify other molecular partners as targets for new interventions. Full article
(This article belongs to the Special Issue Breast Cancer: New Diagnostic and Therapeutic Approaches)
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12 pages, 719 KiB  
Article
Analysis of Circulating Catestatin in Early Pregnancy: A Preliminary Investigation
by Zdenka Sunjic Lovric, Jasminka Resic Karara, Bianka Mimica, Marko Kumric, Daniela Supe-Domic, Roko Santic and Josko Bozic
Biomedicines 2024, 12(11), 2626; https://doi.org/10.3390/biomedicines12112626 - 16 Nov 2024
Viewed by 338
Abstract
Background: During pregnancy, significant cardiovascular changes occur to accommodate fetal growth, and catestatin may play a role in these changes. Evidence suggests that catestatin, a pleiotropic sympathoinhibitory peptide, is involved in multiple cardiovascular pathologies, including hypertensive disorders. The objective of this study was [...] Read more.
Background: During pregnancy, significant cardiovascular changes occur to accommodate fetal growth, and catestatin may play a role in these changes. Evidence suggests that catestatin, a pleiotropic sympathoinhibitory peptide, is involved in multiple cardiovascular pathologies, including hypertensive disorders. The objective of this study was to compare serum catestatin levels between first-trimester pregnant women and non-pregnant women, aiming to investigate catestatin’s role in blood pressure regulation during early pregnancy. Methods: This cross-sectional study included 72 first-trimester pregnant women and 57 age-matched non-pregnant controls, all without known cardiovascular or metabolic disorders. Results: Serum catestatin concentrations were significantly higher in pregnant women compared to controls (12.4 (9.9–21.2) ng/mL vs. 7.1 (4.5–10.9) ng/mL, p < 0.001). However, there was no significant difference in serum catestatin levels between those with a normal and abnormal uterine artery pulsatility index (17.8 (8.3-22.3) ng/mL vs. 12.5 (9.9–22.4) ng/mL, p = 0.962). Similarly, catestatin concentrations did not significantly differ between primiparous and multiparous women (14.0 (11.5–22.4) ng/mL vs. 10.7 (8.8–19.0) ng/mL). A positive correlation was observed between systolic blood pressure and serum catestatin levels in the control group (r = 0.335, p = 0.011) but not in pregnant women. Conclusions: Research on catestatin in pregnancy is still in its early stages, necessitating further studies to fully elucidate its roles and potential therapeutic applications. Full article
(This article belongs to the Section Molecular and Translational Medicine)
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19 pages, 4547 KiB  
Article
p75NTR Modulation Reduces Oxidative Stress and the Expression of Pro-Inflammatory Mediators in a Cell Model of Rett Syndrome
by Michela Varone, Giuseppe Scavo, Mayra Colardo, Noemi Martella, Daniele Pensabene, Emanuele Bisesto, Andrea Del Busso and Marco Segatto
Biomedicines 2024, 12(11), 2624; https://doi.org/10.3390/biomedicines12112624 - 16 Nov 2024
Viewed by 367
Abstract
Background: Rett syndrome (RTT) is an early-onset neurological disorder primarily affecting females, leading to severe cognitive and physical disabilities. Recent studies indicate that an imbalance of redox homeostasis and exacerbated inflammatory responses are key players in the clinical manifestations of the disease. Emerging [...] Read more.
Background: Rett syndrome (RTT) is an early-onset neurological disorder primarily affecting females, leading to severe cognitive and physical disabilities. Recent studies indicate that an imbalance of redox homeostasis and exacerbated inflammatory responses are key players in the clinical manifestations of the disease. Emerging evidence highlights that the p75 neurotrophin receptor (p75NTR) is implicated in the regulation of oxidative stress (OS) and inflammation. Thus, this study is aimed at investigating the effects of p75NTR modulation by LM11A-31 on fibroblasts derived from RTT donors. Methods: RTT cells were treated with 0.1 µM of LM11A-31 for 24 h, and results were obtained using qPCR, immunofluorescence, ELISA, and Western blot techniques. Results: Our findings demonstrate that LM11A-31 reduces OS markers in RTT fibroblasts. Specifically, p75NTR modulation by LM11A-31 restores protein glutathionylation and reduces the expression of the pro-oxidant enzyme NOX4. Additionally, LM11A-31 significantly decreases the expression of the pro-inflammatory mediators interleukin-6 and interleukin-8. Additionally, LM11A-31 normalizes the expression levels of transcription factors involved in the regulation of the antioxidant response and inflammation. Conclusions: Collectively, these data suggest that p75NTR modulation may represent an effective therapeutic target to improve redox balance and reduce inflammation in RTT. Full article
(This article belongs to the Special Issue Antioxidants and Oxidative Stress in Human Health and Diseases)
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4 pages, 199 KiB  
Editorial
Prognostic Value of Circulating Biomarkers of Fibrotic Remodeling in Arrhythmogenic Cardiomyopathy
by Stephen P. Chelko
Biomedicines 2024, 12(11), 2623; https://doi.org/10.3390/biomedicines12112623 - 16 Nov 2024
Viewed by 298
Abstract
Arrhythmogenic cardiomyopathy (ACM) is a nonischemic, familial heart disease with a high risk of sudden cardiac death (SCD) in the pediatric population and accounts for >20% of SCDs worldwide [...] Full article
(This article belongs to the Special Issue Advanced Research in Arrhythmogenic Cardiomyopathy)
38 pages, 531 KiB  
Review
Epigenetics of Hypertensive Nephropathy
by Yize Zhang, Hamidreza Arzaghi, Zhehan Ma, Yasmin Roye and Samira Musah
Biomedicines 2024, 12(11), 2622; https://doi.org/10.3390/biomedicines12112622 - 16 Nov 2024
Viewed by 264
Abstract
Hypertensive nephropathy (HN) is a leading cause of chronic kidney disease (CKD) and end-stage renal disease (ESRD), contributing to significant morbidity, mortality, and rising healthcare costs. In this review article, we explore the role of epigenetic mechanisms in HN progression and their potential [...] Read more.
Hypertensive nephropathy (HN) is a leading cause of chronic kidney disease (CKD) and end-stage renal disease (ESRD), contributing to significant morbidity, mortality, and rising healthcare costs. In this review article, we explore the role of epigenetic mechanisms in HN progression and their potential therapeutic implications. We begin by examining key epigenetic modifications—DNA methylation, histone modifications, and non-coding RNAs—observed in kidney disease. Next, we discuss the underlying pathophysiology of HN and highlight current in vitro and in vivo models used to study the condition. Finally, we compare various types of HN-induced renal injury and their associated epigenetic mechanisms with those observed in other kidney injury models, drawing inferences on potential epigenetic therapies for HN. The information gathered in this work indicate that epigenetic mechanisms can drive the progression of HN by regulating key molecular signaling pathways involved in renal damage and fibrosis. The limitations of Renin–Angiotensin–Aldosterone System (RAAS) inhibitors underscore the need for alternative treatments targeting epigenetic pathways. This review emphasizes the importance of further research into the epigenetic regulation of HN to develop more effective therapies and preventive strategies. Identifying novel epigenetic markers could provide new therapeutic opportunities for managing CKD and reducing the burden of ESRD. Full article
(This article belongs to the Special Issue Genetic and Epigenetics of Kidney Development: Pathologies of Renal Anomalies and Kidney Diseases)
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15 pages, 1648 KiB  
Article
Effect of Comparable Carbon Chain Length Short- and Branched-Chain Fatty Acids on Adipokine Secretion from Normoxic and Hypoxic Lipopolysaccharide-Stimulated 3T3-L1 Adipocytes
by Ala Alzubi and Jennifer M. Monk
Biomedicines 2024, 12(11), 2621; https://doi.org/10.3390/biomedicines12112621 - 16 Nov 2024
Viewed by 349
Abstract
Background: Microbial fermentation of non-digestible carbohydrates and/or protein produces short-chain fatty acids (SCFA), whereas branched-chain fatty acids (BCFA) are produced from protein fermentation. The effects of individual SCFA and BCFA of comparable carbon chain length on adipocyte inflammation have not been investigated. Objective [...] Read more.
Background: Microbial fermentation of non-digestible carbohydrates and/or protein produces short-chain fatty acids (SCFA), whereas branched-chain fatty acids (BCFA) are produced from protein fermentation. The effects of individual SCFA and BCFA of comparable carbon chain length on adipocyte inflammation have not been investigated. Objective: To compare the effects of SCFA and BCFA on inflammatory mediator secretion in an adipocyte cell culture model designed to recapitulate obesity-associated adipocyte inflammation under normoxic and hypoxic conditions. Methods: The 3T3-L1 adipocytes were cultured (24 h) without (Control, Con) and with 1 mmol/L of SCFA (butyric acid (But) or valeric acid (Val)) or 1 mmol/L of BCFA (isobutyric acid (IsoBut) or isovaleric acid (IsoVal)) and were unstimulated (cells alone, n = 6/treatment), or stimulated with 10 ng/mL lipopolysaccharide (LPS, inflammatory stimulus, n = 8/treatment) or 10 ng/mL LPS + 100 µmol/L of the hypoxia memetic cobalt chloride (LPS/CC, inflammatory/hypoxic stimulus, n = 8/treatment). Results: Compared to Con + LPS, But + LPS reduced secreted protein levels of interleukin (IL)-1β, IL-6, macrophage chemoattractant protein (MCP)-1/chemokine ligand (CCL)2, MCP3/CCL7, macrophage inflammatory protein (MIP)-1α/CCL3 and regulated upon activation, normal T cell expressed, and secreted (RANTES)/CCL5 and decreased intracellular protein expression of the ratio of phosphorylated to total signal transducer and activator of transcription 3 (STAT3) and nuclear factor kappa B (NFκB) p65 (p < 0.05). Val + LPS reduced IL-6 secretion and increased MCP-1/CCL2 secretion compared to Con + LPS and exhibited a different inflammatory mediator secretory profile from But + LPS (p < 0.05), indicating that individual SCFA exert individual effects. There were no differences in the secretory profile of the BCFA IsoBut + LPS and IsoVal + LPS (p > 0.05). Alternatively, under inflammatory hypoxic conditions (LPS/CC) Val, IsoVal, and IsoBut all increased secretion of IL-6, MCP-1/CCL2 and MIP-1α/CCL3 compared to Con (p < 0.05), whereas mediator secretion did not differ between But and Con (p > 0.05), indicating that the proinflammatory effects of SCFA and BCFA was attenuated by But. Interestingly, But + LPS/CC decreased STAT3 activation versus Con + LPS/CC (p < 0.05). Conclusions: The decreased secretion of inflammatory mediators that is attributable to But highlights the fact that individual SCFA and BCFA exert differential effects on adipocyte inflammation under normoxic and hypoxic conditions. Full article
(This article belongs to the Special Issue Recent Advances in Adipokines—2nd Edition)
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Brief Report
Short-Cycle Therapy with Bictegravir/Emtricitabine/Tenofovir Alafenamide in a Small Cohort of Virally Suppressed People Living with HIV: A Long-Term Follow-Up
by Massimiliano Lanzafame, Emanuela Lattuada, Andrea Delama, Giovanni Mori and Sandro Vento
Biomedicines 2024, 12(11), 2620; https://doi.org/10.3390/biomedicines12112620 - 15 Nov 2024
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Abstract
Background: Antiretroviral triple therapy has considerably reduced morbidity and mortality in people living with HIV and is the standard-of-care treatment. However, it is lifelong and linked to long-term side effects and adherence problems. Methods: Here, we report long-term virological and immunological outcome in [...] Read more.
Background: Antiretroviral triple therapy has considerably reduced morbidity and mortality in people living with HIV and is the standard-of-care treatment. However, it is lifelong and linked to long-term side effects and adherence problems. Methods: Here, we report long-term virological and immunological outcome in 12 virally suppressed people on short-cycle therapy with bictegravir/emtricitabine/tenofovir alafenamide administered five days a week (Monday to Friday). Results: All patients, after a long term follow-up, were virally suppressed Conclusions: In the wait for new long-acting antiretroviral drugs and new antiretroviral formulations, short-cycle therapy has proven to be a safe and effective alternative to the standard daily antiretroviral regimen for individuals living with HIV who are virologically suppressed. Full article
(This article belongs to the Special Issue Progress in Antiretroviral Research)
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