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22 pages, 1395 KB  
Review
Extracellular Matrix Remodeling and Matrix Metalloproteinases in Ovarian Function and Infertility
by Efthalia Moustakli, Athanasios Zikopoulos, Periklis Katopodis, Vasilios Sebastian Paraschos, Ioannis Messinis and Christina Messini
Int. J. Mol. Sci. 2026, 27(8), 3652; https://doi.org/10.3390/ijms27083652 (registering DOI) - 19 Apr 2026
Abstract
Ovarian function relies on a network of well-coordinated molecular mechanisms that regulate follicular development, oocyte maturation, ovulation, and corpus luteum function. When these processes are disrupted, infertility can result. Extracellular matrix (ECM) remodeling represents a central regulatory component in these processes and is [...] Read more.
Ovarian function relies on a network of well-coordinated molecular mechanisms that regulate follicular development, oocyte maturation, ovulation, and corpus luteum function. When these processes are disrupted, infertility can result. Extracellular matrix (ECM) remodeling represents a central regulatory component in these processes and is essential for follicle rupture and oocyte release. This mechanism involves metalloproteinases (MMPs), mainly MMP-2 and MMP-9, which degrade the ECM and allow the necessary structural changes. Other ECM-modulating proteases, such as ADAM and ADAMTS families, also contribute to this process. Their activity is tightly regulated by tissue inhibitors of metalloproteinases (TIMPs), ensuring that tissue remodeling occurs in a controlled manner. Disruption of the balance between MMPs and TIMPs increases the risk of infertility-related conditions such as polycystic ovary syndrome (PCOS), endometriosis, luteinizing hormone (LH) deficiency syndrome, and ovarian aging. In addition to the ECM, other factors, including intracellular signaling pathways, oxidative stress (OS), and mitochondrial function, contribute to ovarian physiology and directly affect oocyte quality and viability. This narrative review focuses on the molecular mechanisms governing ovarian function, with particular emphasis on the remodeling of the ECM by MMPs during ovulation, and examines how their disorders contribute to infertility. A deeper understanding of these mechanisms may lead to the identification of new therapeutic targets and the improvement of assisted reproduction outcomes. Full article
(This article belongs to the Special Issue Molecular Pathways to Infertility)
12 pages, 500 KB  
Article
Effects of Intraoperative Prone Versus Supine Positioning on Postoperative Delirium
by Theresa E. Hering, Maria Wittmann, Vera Guttenthaler, Robert Pflugmacher and Rudolf Hering
Geriatrics 2026, 11(2), 48; https://doi.org/10.3390/geriatrics11020048 (registering DOI) - 19 Apr 2026
Abstract
Background: Postoperative delirium (POD) is a common complication in geriatric patients. This prospective cohort study evaluated a possible influence of intraoperative positioning on the occurrence of POD, as intraoperative prone positioning could affect cerebral perfusion. Methods: We included 760 patients of ³60 [...] Read more.
Background: Postoperative delirium (POD) is a common complication in geriatric patients. This prospective cohort study evaluated a possible influence of intraoperative positioning on the occurrence of POD, as intraoperative prone positioning could affect cerebral perfusion. Methods: We included 760 patients of ³60 years scheduled for elective surgery in prone or supine positions. The primary outcome was POD incidence on the first five days after surgery, assessed via 3D-Confusion Assessment Method (3-D CAM) or Confusion Assessment Method for Intensive Care Units (CAM-ICU). Preoperative assessments included the American Society of Anesthesiologists (ASA) and New York Heart Association (NYHA) classifications as well as short screenings for the cognitive (modified Montreal Cognitive Assessment (MoCA)) and self-care status of the patient. Secondary outcomes were length of hospital stay (LOS) and mortality rates. Results: Postoperative delirium rates were similar in prone and supine patients (7.6% vs. 5.5%; p = 0.31), and logistic regression analysis revealed no association of intraoperative prone positioning with POD (odds ratio 1.42 (95% CI 0.68–2.92; p = 0.342)). The overall incidence of POD was 6.1% and was associated with older age (81.5 (CI 76.2–84.8) vs. 72.0 (CI 67.0–79.0) years; p < 0.01), higher ASA and NHYA classifications, lower preoperative modified MoCA, reduced independence in self-care (p < 0.001, respectively), and longer incision-to-suture times (107.0 (CI 73.0–173.0) vs. 85.0 (CI 60.0–130.0) minutes; p < 0.01). Postoperative delirium resulted in longer LOS (14.5 (CI 9.0–27.0) vs. 7.0 (CI 4.0–9.0) days; p < 0.001), and increased mortality (13.0% vs. 1.7%; p < 0.001). Conclusions: Intraoperative prone positioning was not associated with POD in patients aged 60 years or older (OR 1.42; CI 0.68–2.92; p < 0.340), and LOS and mortality as secondary outcome parameters were also similar in patients after prone and supine surgery. Future studies assessing additional and possible confounding factors and intraoperative systemic and regional hemodynamics and oxygenation are needed to verify this result and to evaluate cerebral hypoperfusion as a possible mechanism of POD. Full article
20 pages, 827 KB  
Review
Targeting the NLRP3 Inflammasome in Atherosclerosis: A Review of Natural Products and Their Molecular Mechanisms
by Su-Jin Bae, Hye-Min Seo, Si-Eon You and Jun-Ho Lee
Int. J. Mol. Sci. 2026, 27(8), 3650; https://doi.org/10.3390/ijms27083650 (registering DOI) - 19 Apr 2026
Abstract
Atherosclerotic cardiovascular disease (ASCVD) is increasingly recognized not merely as a lipid-storage disorder but as a chronic, lipid-driven inflammatory condition of the arterial wall. Despite the widespread use of statins and other lipid-lowering therapies, a substantial “residual inflammatory risk” persists, propelling the search [...] Read more.
Atherosclerotic cardiovascular disease (ASCVD) is increasingly recognized not merely as a lipid-storage disorder but as a chronic, lipid-driven inflammatory condition of the arterial wall. Despite the widespread use of statins and other lipid-lowering therapies, a substantial “residual inflammatory risk” persists, propelling the search for targeted immunopharmacological interventions. At the forefront of this inflammatory cascade is the nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome, which serves as a central orchestrator of vascular inflammation by linking metabolic dysregulation to the innate immune response. Atherogenic danger signals—such as oxidized low-density lipoprotein (ox-LDL) and cholesterol crystals—trigger NLRP3 activation through reactive oxygen species (ROS) generation, lysosomal rupture, and potassium efflux. This, in turn, drives the maturation of pro-inflammatory cytokines (IL-1β and IL-18) and initiates macrophage pyroptosis. In this review, we systematically evaluate the immunomodulatory potential of natural products—both complex extracts and single bioactive compounds—in inhibiting the NLRP3 inflammasome axis. We detail the pharmacological mechanisms by which these natural agents intercept inflammatory signaling at multiple stages: suppressing TLR4/NF-κB-mediated priming, scavenging mitochondrial ROS, and restoring autophagic flux via AMPK/mTOR pathways to prevent inflammasome assembly. By critically analyzing these pathways, we highlight natural product-derived inhibitors as a promising class of immunomodulators capable of attenuating atherosclerotic progression and addressing the persistent challenge of residual inflammatory risk. Full article
(This article belongs to the Section Bioactives and Nutraceuticals)
26 pages, 435 KB  
Review
Exploring the Senotherapeutic Potential of Polyphenols in Aging and Disease: A Literature Review
by Luna Braučič Mitrovic and Khrystyna O. Semen
Int. J. Mol. Sci. 2026, 27(8), 3651; https://doi.org/10.3390/ijms27083651 (registering DOI) - 19 Apr 2026
Abstract
Aging is associated with an increased risk of developing many age-related diseases (ARDs), which are of major global health concern. In recent years, cellular senescence, characterized by cell cycle arrest and development of a senescence-associated secretory phenotype (SASP), has emerged as a key [...] Read more.
Aging is associated with an increased risk of developing many age-related diseases (ARDs), which are of major global health concern. In recent years, cellular senescence, characterized by cell cycle arrest and development of a senescence-associated secretory phenotype (SASP), has emerged as a key mechanism of aging and ARDs and has been increasingly explored as a promising therapeutic target. Among dietary bioactive ingredients, fisetin and quercetin have gained attention because of their potential to act as senolytics and senomorphics. This narrative literature review summarizes existing evidence exploring the potential of fisetin and quercetin to modulate senescence and SASP biomarkers in animal models of aging and progeria, as well as in interventional studies involving human subjects with geriatric syndromes and/or various ARDs. It also provides a brief overview of the molecular mechanisms of senescence and attempts to identify potential drivers and barriers for the clinical translation of those nutrients. Full article
22 pages, 3718 KB  
Article
Photovoltaic Sub-Synchronous Oscillation Suppression Method Based on Model-Free Adaptive Control
by Chaojun Zheng, Xiu Yang and Chenyang Zhao
Energies 2026, 19(8), 1977; https://doi.org/10.3390/en19081977 (registering DOI) - 19 Apr 2026
Abstract
The large-scale grid integration of photovoltaic systems, accompanied by extensive power electronic equipment, exacerbates the risk of sub-synchronous oscillation (SSO) and poses a serious threat to the safe and stable operation of modern power systems. To address the limitation that traditional additional damping [...] Read more.
The large-scale grid integration of photovoltaic systems, accompanied by extensive power electronic equipment, exacerbates the risk of sub-synchronous oscillation (SSO) and poses a serious threat to the safe and stable operation of modern power systems. To address the limitation that traditional additional damping controllers rely on accurate mathematical models of the system, this paper applies model-free adaptive control (MFAC) to suppress sub-synchronous oscillation in photovoltaic systems. The proposed method requires no prior identification of the plant model and achieves adaptive control by online estimation of pseudo-partial derivatives using only system input-output data, with parameters optimized by particle swarm optimization. Simulation results show that the proposed controller can effectively shorten the settling time and suppress oscillations However, for oscillations induced by different mechanisms, it still has the limitation of requiring parameter re-optimization. This approach provides a new model-free technical pathway for sub-synchronous oscillation mitigation in grid-connected photovoltaic systems. Full article
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13 pages, 615 KB  
Article
Performance of Traditional Cardiovascular Risk Scores and Objective Optimization in Cancer Survivors
by Harsh A. Patel, Saifullah Syed, Pranathi Tella, Harshith Thyagaturu and Brijesh Patel
Curr. Oncol. 2026, 33(4), 230; https://doi.org/10.3390/curroncol33040230 (registering DOI) - 19 Apr 2026
Abstract
Introduction: Cardiovascular disease (CVD) is a leading cause of non-cancer death among cancer survivors, attributable to cardiotoxic therapies and cardiovascular risk factors. General population risk prediction tools, including ASCVD (Atherosclerotic cardiovascular disease), Framingham’s Score, and PREVENT (Predicting Risk of Cardiovascular Disease EVENTS), lack [...] Read more.
Introduction: Cardiovascular disease (CVD) is a leading cause of non-cancer death among cancer survivors, attributable to cardiotoxic therapies and cardiovascular risk factors. General population risk prediction tools, including ASCVD (Atherosclerotic cardiovascular disease), Framingham’s Score, and PREVENT (Predicting Risk of Cardiovascular Disease EVENTS), lack cancer-specific variables. We evaluated whether these models, even after statistical optimization, could predict cardiovascular mortality in cancer survivors. Methods: Using the National Health and Nutrition Examination Survey (NHANES) 2001–2018, linked with National Death Index (NDI) mortality data, we conducted a retrospective analysis of 634 and 429 cancer survivors, respectively, across model-specific cohorts free of baseline cardiovascular disease. Discrimination was assessed for ASCVD, Framingham Score, and PREVENT using standardized thresholds of 7.5% and 20%, as well as Youden-optimized cutoffs. Area under the curve (AUC) comparisons were performed using the DeLong non-parametric method. Results: Standard thresholds showed suboptimal discrimination across all models (AUCs: ASCVD 0.56, Framingham 0.53, PREVENT 0.64). In contrast, Youden-optimized AUCs (ASCVD: 0.68; PREVENT: 0.71; all p < 0.001, DeLong test). Optimization increased the “low-risk” group’s mortality rate from 2.8% to 4.1% (RR = 1.47), suggesting improved statistical fit came at the cost of overestimating the risk. Optimized thresholds outperformed conventional cutoffs, underscoring the necessity for recalibrated, cohort-specific risk stratification in cancer survivors. Conclusions: Standard risk scores have inadequate discrimination for cardiovascular mortality prediction in cancer survivors. Threshold recalibration improves statistical metrics but does not resolve the structural failure of these models to account for cardiotoxic exposure. Development of cardio-oncology-specific risk models incorporating oncologic exposures is therefore warranted. Full article
31 pages, 7683 KB  
Review
Prostate Cancer Diagnostics in Transition: A Review of Promising Biomarkers, Multiplex Biosensors, and Point-of-Care Diagnostic Strategies
by Sarra Takita, Alexei Nabok, Magdi H. Mussa, Abdalrahem Shtawa, Anna Lishchuk and David P. Smith
Chemosensors 2026, 14(4), 99; https://doi.org/10.3390/chemosensors14040099 (registering DOI) - 19 Apr 2026
Abstract
Prostate cancer (PCa) remains one of the most prevalent urological malignancies worldwide, with early and accurate diagnosis being critical for improving patient outcomes. Traditional screening approaches, such as digital rectal examination and prostate-specific antigen (PSA) testing, have long served as frontline tools; however, [...] Read more.
Prostate cancer (PCa) remains one of the most prevalent urological malignancies worldwide, with early and accurate diagnosis being critical for improving patient outcomes. Traditional screening approaches, such as digital rectal examination and prostate-specific antigen (PSA) testing, have long served as frontline tools; however, their limited specificity and sensitivity contribute to high rates of false positives, unnecessary biopsies, and overtreatment. Recent UK guidelines and international consensus increasingly question the role of PSA-based population screening, advocating for risk-stratified pathways and multiparametric MRI as first-line investigations. In parallel, advances in molecular biology have identified promising cancer-specific biomarkers, such as prostate cancer antigen 3 (PCA3) and transmembrane protease serine 2 (TMPRSS2:ERG), that outperform PSAs in terms of specificity and prognostic value. These developments have catalysed innovation in biosensor technologies, enabling rapid, cost-effective, and non-invasive detection of single and multiplex biomarkers in urine and serum. Electrochemical and optical affinity-based biosensors offer transformative potential for the development of personalised point-of-care platforms and diagnostics, reducing the reliance on invasive procedures and improving clinical decision-making. The latter can be augmented with artificial intelligence (AI) tools. This review critically examines the limitations of PSAs, synthesises evidence on novel biomarkers and imaging-led strategies, and evaluates the design, performance, and translational challenges of biosensor-based assays. Furthermore, it outlines future directions, including standardisation, large-scale clinical validation, and integration of multiplex biosensors with AI for precision diagnostics. By bridging molecular insights with engineering innovations, these approaches promise to redefine PCa screening and enable accurate, patient-centred care. Full article
(This article belongs to the Special Issue Electrochemical Biosensors for Global Health Challenges)
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23 pages, 15269 KB  
Article
From Local Tissue Repair to Fibrosis: Deciphering Gene Co-Expression Networks in Benign Pulmonary Nodules and Idiopathic Pulmonary Fibrosis Comorbidity via Bioinformatics and Machine Learning
by Yaoyu Xie, Jingzhe Gao, Yifan Ren, Xiaoran Sun, Siju Lou, Guangli Yan, Ning Zhang, Hui Sun and Xijun Wang
Int. J. Mol. Sci. 2026, 27(8), 3647; https://doi.org/10.3390/ijms27083647 (registering DOI) - 19 Apr 2026
Abstract
With increasing environmental pollution and a high incidence of respiratory infections, pulmonary nodules (PN) are being detected more frequently. Although most are benign, they are often accompanied by chronic inflammation and localized fibrosis, which may predispose patients to progression toward idiopathic pulmonary fibrosis [...] Read more.
With increasing environmental pollution and a high incidence of respiratory infections, pulmonary nodules (PN) are being detected more frequently. Although most are benign, they are often accompanied by chronic inflammation and localized fibrosis, which may predispose patients to progression toward idiopathic pulmonary fibrosis (IPF). However, the biological relationship between benign pulmonary nodules (BPNs) and IPF remains poorly understood. Therefore, this study aims to investigate the shared molecular mechanisms and identify potential biomarkers linking BPN and IPF, with the goal of elucidating the pathogenic transition from BPN to IPF. In this study, microarray data from GEO datasets were systematically analyzed to explore shared molecular mechanisms, immune infiltration characteristics, and potential early intervention strategies linking BPN and IPF. Differential expression analysis, protein–protein interaction (PPI) networks, weighted gene co-expression network analysis (WGCNA), and integrative machine learning approaches identified MME and ANKRD23 as key hub genes associated with the transition from BPN to IPF. Both genes demonstrated strong diagnostic performance, with Area Under the Curve (AUC) values exceeding 0.7, and were significantly correlated with immune cell infiltration, particularly effector memory CD8+ T cells. Functional enrichment and gene set enrichment analyses indicated that these genes were mainly involved in immune-related processes in BPN, while in IPF, ANKRD23 was linked to cytoskeletal organization and genomic stability, and MME was enriched in profibrotic pathways such as TGF-β signaling. The diagnostic value of these biomarkers was further validated in a bleomycin-induced IPF mouse model using quantitative polymerase chain reaction (qPCR). In addition, drug–gene interaction prediction and molecular docking analyses highlighted several naturally derived compounds with favorable binding affinity and anti-inflammatory properties, among which folic acid, curcumin, and arbutin emerged as promising candidates for safe early intervention. Collectively, these findings identify MME and ANKRD23 as potential biomarkers for early identification of BPN patients at risk of developing IPF and provide a theoretical basis for early diagnosis and targeted preventive strategies. Full article
(This article belongs to the Special Issue Benchmarking of Modeling and Informatic Methods in Molecular Sciences)
15 pages, 13809 KB  
Article
Computed Tomography-Based Morphometric Analysis of the Ascending Aorta in Acute Type A Dissection Beyond Diameter-Based Thresholds: A National Cohort Study from Latvia
by Ivars Brecs, Sandra Skuja, Simons Svirskis, Nityanand Jain and Peteris Stradins
Med. Sci. 2026, 14(2), 204; https://doi.org/10.3390/medsci14020204 (registering DOI) - 19 Apr 2026
Abstract
Background/Objectives: Ascending aortic aneurysm is a heterogeneous disease, with many cases of acute Stanford type A aortic dissection (ATAAD) presenting with aortic diameters below currently recommended surgical thresholds. Demographic factors such as age and sex, along with indexed aortic size groups, have [...] Read more.
Background/Objectives: Ascending aortic aneurysm is a heterogeneous disease, with many cases of acute Stanford type A aortic dissection (ATAAD) presenting with aortic diameters below currently recommended surgical thresholds. Demographic factors such as age and sex, along with indexed aortic size groups, have been proposed to improve risk stratification. Methods: We included 65 adult patients who underwent surgical intervention for ATAAD. Morphometric measurements were obtained from computed tomography angiography (CTA) using centerline reconstruction. Maximum ascending aortic diameter and length were measured. Indexed parameters included the aortic size index (ASI), aortic height index (AHI), aortic length index (ALI) and cross-sectional aortic area indexed to height (CSA/H). Estimated pre-dissection dimensions were derived by reducing diameter by 18% and length by 2.7%. The cohort was stratified by age-, sex-, and ASI-defined groups. Results: Women were older than men (mean age 67 [SD 11] vs. 58 [SD 13] years, p = 0.01). Aortic diameter and length did not differ significantly by age or sex. At presentation, an ascending aortic diameter < 5.0 cm was observed in 37.1% of patients aged < 65 years and 26.7% of those aged ≥ 65 years. When stratified by sex, 25.0% of women and 35.6% of men presented with an ascending aortic diameter < 5.0 cm. Indexed parameters (ALI, AHI and ASI) were higher in older patients and women despite their smaller body size. In estimated pre-dissection analyses, less than 10% of the patients had diameters ≥ 5.5 cm, whereas most had estimated diameters < 5.0 cm. Conclusions: A substantial proportion of patients with ATAAD present with aortic dimensions below the current surgical thresholds. These findings underscore the limitations of diameter-based criteria and support the potential value of indexed geometric parameters in improving risk assessment in ATAAD patients. Full article
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