Search Results (2,817)

Cardiovascular disease remains the leading cause of mortality worldwide, and at its molecular core lies a silent disruptor: oxidative stress. This imbalance between reactive oxygen species (ROS) and antioxidant defenses not only damages cellular components but also orchestrates a cascade of pathological events across diverse cardiac cell types. In cardiomyocytes, ROS overload impairs contractility and survival, contributing to heart failure and infarction. Cardiac fibroblasts respond by promoting fibrosis through excessive collagen deposition. Macrophages intensify inflammatory responses, such as atherosclerosis, via ROS-mediated lipid oxidation—acting both as mediators of damage and targets for antioxidant intervention. This review examines how oxidative stress affects cardiac cell types and evaluates antioxidant-based therapeutic strategies. Therapeutic approaches include natural antioxidants (e.g., polyphenols and vitamins) and synthetic agents (e.g., enzyme modulators), which show promise in experimental models by improving myocardial remodeling. However, clinical trials reveal inconsistent outcomes, underscoring translational challenges (e.g., clinical biomarkers). Emerging strategies—such as targeted antioxidant delivery, activation of endogenous pathways, and disease modeling using 3D organoids—aim to enhance efficacy. In conclusion, we spotlight innovative technologies—like lab-grown heart tissue models—that help scientists better understand how oxidative stress affects heart health. These tools are bridging the gap between early-stage research and personalized medicine, opening new possibilities for diagnosing and treating heart disease more effectively. Full article

Background: Patient satisfaction with diabetes technology is increasingly recognized as a key factor in therapeutic success. Patient-reported outcomes (PROs) are gaining importance in diabetes care and in the evaluation of advanced insulin delivery systems. Objectives: This study aimed to design and validate a new questionnaire, the Insulin Pump Infusion Sets Satisfaction Scale (IPISS), to assess satisfaction with insulin infusion sets among individuals with type 1 diabetes. Methods: The questionnaire was developed by our Diabetology Unit in two versions: one for patient self-reporting and one for caregivers when the patient is too young to complete it autonomously. Content validity was assessed by six healthcare professionals (three diabetologists and three nurses) based on Polit and Beck’s methodology. The Item Content Validity Index (I-CVI) was calculated for both relevance and comprehensibility and was considered satisfactory if expert agreement reached ≥83%. The Scale Content Validity Index (S-CVI) was computed as the average of I-CVIs, with a cut-off value > 90% deemed acceptable. Results: Almost all items achieved 100% positive agreement for both relevance and comprehensibility, except one item in the caregiver version, for which one rater did not provide a rating for comprehensibility (I-CVI = 83.3%). The S-CVI was 100% for relevance in both versions, 99.24% for comprehensibility in the caregiver version, and 100% in the patient version. Conclusions: The IPISS is a content-validated, self-reported tool, suitable for evaluating satisfaction with infusion sets in individuals using insulin pumps, with versions adapted for both patients and caregivers. Full article

Audiovisual Entrainment (AVE) is a non-invasive, non-pharmacological neuromodulation approach that aims to align brain activity with externally delivered auditory and visual rhythms. This review surveys AVE’s historical development, technical parameters (e.g., frequency, phase, waveform, color, intensity, presentation mode), components and delivery methods, reported clinical applications, and safety considerations. Given the heterogeneity of AVE protocols and terminology, we conducted a structured narrative review (PubMed, Scopus, Google Scholar; earliest records to July 2025), including human and animal studies that met an operational definition of regulated AVE and consistent administration of specified auditory and visual frequencies, with critical methodological details reported. We highlight AVE’s accessibility and versatility, outline a stepwise parameter reporting framework to support standardization, and discuss putative mechanisms via sensory and oscillatory pathways. However, current findings are heterogeneous and include null or limited effects. Mechanistic understanding and parameter optimization remain insufficiently developed, and premature claims of efficacy are not warranted. Rigorous, standardized, and adequately controlled studies are needed before AVE can be considered a reliable therapeutic tool. Full article

Today, science and medicine are striving to develop novel techniques for treating deadly diseases, including a wide range of cancers. Efforts are being made to better understand the molecular and biochemical mechanisms of tumor cell functioning, but a particular emphasis has recently been given to investigating immune cells residing in the tumor microenvironment, which may lead to revolutionary benefits in the design of new immunotherapies. Among these cells, tumor-associated macrophages (TAMs) are highly abundant and act as critical regulators of ovarian cancer progression, metastasis, and resistance to therapy. Their dual nature—as drivers of malignancy and as potential therapeutic mediators—has positioned them at the forefront of research into next-generation immunotherapies. As therapeutic targets, approaches include blocking macrophage recruitment (e.g., CSF-1/CSF-1R inhibitors), selectively depleting subsets of TAMs (e.g., via Folate Receptor Beta), or reprogramming immunosuppressive M2-like macrophages toward an anti-tumor M1 phenotype. On the other hand, macrophages can also serve as a therapeutic tool—they may be engineered to enhance anti-tumor immunity, as exemplified by the development of Chimeric Antigen Receptor Macrophages (CAR-Ms), or leveraged as delivery vehicles for targeted drug transport into the tumor microenvironment. A particularly innovative strategy involves Macrophage–Drug Conjugates (MDCs), which employs the transfer of iron-binding proteins (TRAIN) mechanism for precise intracellular delivery of therapeutic agents, thereby enhancing drug efficacy while minimizing systemic toxicity. This review integrates current knowledge of TAM biology, highlights emerging therapeutic approaches, and underscores the promise of macrophage-based interventions in ovarian cancer. By integrating macrophage-targeting strategies with advanced immunotherapeutic platforms, novel treatment paradigms may be determined that could substantially improve outcomes for patients with ovarian cancer and other solid tumors. Our work highlights that macrophages should be a particular area of research interest in the context of cancer treatment. Full article

Background and Objective: Postpartum depression (PPD) is a prevalent psychiatric condition with significant consequences for maternal, paternal, and infant well-being. In Saudi Arabia, some reported prevalence rates exceed global averages. This narrative review synthesizes the current literature on the prevalence, risk factors, awareness, and quality-of-life impact of PPD in Saudi Arabia. The aim is to identify methodological inconsistencies, highlight the risk factors, and guide future research and policy. Method: A comprehensive literature search was conducted using PubMed, Scopus, Web of Science, and Google Scholar. Studies published between 2010 and May 2025 were included if they addressed PPD in Saudi Arabia and the inclusion criteria were met. 38 articles were selected for full-text analysis and incorporation in the study. Results: PPD prevalence in Saudi Arabia ranges from 5.1% to 75.7%, with regional variation attributed to inconsistent methodologies, screening instruments, and diagnostic cutoffs. Risk factors encompass psychiatric history, marital conflict, limited social support, low income, cesarean delivery, unplanned pregnancy, anemia, and sleep disturbance. Nutritional and newborn-related predictors were inconsistently reported. Awareness among the public and healthcare professionals remains limited, and paternal postpartum depression is underrecognized. PPD exerts a pronounced negative impact on maternal quality of life, spanning physical, psychological, and social domains. Conclusions: PPD poses a substantial public health burden in Saudi Arabia. Routine screening with validated tools, integrated perinatal mental health services, and targeted public education campaigns may help address diagnostic delays and stigma. Future studies must adopt standardized diagnostic criteria and longitudinal designs to generate nationally representative prevalence estimates and evaluate preventive strategies. Full article

Alzheimer’s disease (AD) represents the major cause of dementia worldwide, involving different etiopathogenetic mechanisms, but with no definitive cure. The efficacy of new AD drugs is limited by the multifactorial disease nature that involves several targets, but also by the difficult penetration across the blood–brain barrier (BBB) for reaching the target area at therapeutic doses. Thus, the inability of many compounds to efficiently bypass the BBB makes it arduous to treat the disease. Furthermore, the lack of more representative BBB in vitro models than conventional 2D cultures, and xenogeneic animal models that recapitulate AD pathogenesis, makes it even more difficult to develop definitive cures. In this context, microfluidics has emerged as a promising tool, offering advanced strategies for simulating the BBB, investigating its crossing mechanisms, and developing nanocarriers that successfully pass the BBB for brain-targeting, with particular interest in pathological states. The advantages of microfluidic platforms for studying the BBB role in pathophysiological conditions might herald more tailored and effective approaches based on functionalized nanosystems for treating AD. Here, we provide an overview of the latest advances in microfluidic-based technologies both for the synthesis of nanodrug delivery systems, and for developing advanced models of the BBB-on-a-chip to simulate this biological barrier, facing open challenges in AD, and improving our understanding of the disease. Full article

Introduction: Cancer cachexia is associated with systemic inflammation and metabolic derangement, leading to muscle atrophy, which affects over 80% of pancreatic cancer patients, the highest rate among all malignancies, negatively impacting quality of life and significantly reducing survival rate. Malnutrition, skeletal muscle loss (sarcopenia), and imbalanced energy expenditure are indicators of cachexia. No established screening tools in clinical practice are specific and sensitive enough to detect pancreatic cancer in its early stages. Objective: This paper aims to provide new insights by examining contributing factors in the development of cachexia and exploring future directions for managing cachexia to improve quality of life and overall survival in patients with pancreatic cancer. Conclusions: It is clinically vital to identify nutritional risks and consider aggressive nutritional interventions as soon as pancreatic cancer is diagnosed to (1) stabilize body weight, (2) decrease the disease-associated burden, and (3) improve the quality of life. To support the clinical management of cachexia in this population, more research is needed. Specifically, research is needed to identify biomarkers, such as muscle fiber-related genes, optimize drug delivery tailored to the specific metabolic and molecular profile, combine chemotherapeutic agents with nutritional supplements, and consider non-pharmacological interventions such as acupuncture and exercise specifically for cancer-cachexia patients. A multifaceted approach will help achieve a better quality of life and prolonged overall survival in patients with pancreatic cancer. Full article

This paper presents an advanced, adaptive model for designing and optimizing agile and sustainable supply chains by integrating fuzzy multi-objective programming, Internet of Things (IoT), digital twin (DT) technologies, and reinforcement learning. Unlike conventional static models, the proposed framework utilizes real-time data and dynamically updates fuzzy parameters through a deep deterministic policy gradient (DDPG) algorithm. The model simultaneously addresses three conflicting objectives: minimizing cost, delivery time, and carbon emissions, while maximizing agility. To validate the model’s effectiveness, various optimization strategies including NSGA-II, MOPSO, and the Whale Optimization Algorithm are applied across small- to large-scale scenarios. Results demonstrate that the integration of IoT and DT, alongside adaptive learning, significantly improves decision accuracy, responsiveness, and sustainability. The model is particularly suited for high-volatility environments, offering decision-makers an intelligent, real-time support tool. Case study simulations further illustrate the model’s value in sectors such as urban logistics and humanitarian aid supply chains. Full article

Cyclodextrin-based nanosponges (CDNSs) are novel polymers composed of cross-linked cyclodextrin (CD) macrocyclic units, whose characteristics make them great candidates for drug delivery systems with adjustable properties for the drug release process. Examination of the molecular structure and dynamics of CDNSs is a necessary starting point in the first step toward their broad application. Spectroscopic methods are effective analytical tools for probing the structure–property relationships of polymer structures. Infrared (IR) and Raman spectroscopies provide insight into the behavior of hydrogen bond (H-bond) networks influencing the properties of CDNS polymeric networks. Scattering techniques such as inelastic neutron scattering (INS) and Brillouin light scattering (BLS) probe elastic properties, while small-angle neutron scattering (SANS) examines the structural inhomogeneities and water sorption abilities of CDNS materials. Complete evaluation is possible using nuclear magnetic resonance (NMR), which can provide data on CDNS network dynamics. This article summarizes the results of a wide examination of CDNSs with the use of spectroscopic methods and reveals the links between the microscopic behavior and macroscopic properties of CDNSs, enabling the customization of their properties for various biomedical purposes. Full article

Adeno-associated virus (AAV) vectors are the preferred gene delivery tool in gene therapy owing to their safety, long-term gene expression, broad tissue tropism, and low immunogenicity. Affinity ligands that can bind multiple AAV serotypes endure harsh clean-in-place (CIP) conditions and are critical for industrial-scale purification. However, current ligands lack broad serotype recognition and adequate alkaline stability, which limits their reusability in large-scale manufacturing. In this study, we employed a competitive biopanning strategy to isolate a single-domain antibody (VHH) that simultaneously binds AAV2, AAV8, and AAV9. The VHH retained structural integrity and binding activity after exposure to 0.1 M NaOH, demonstrating robust alkaline stability. Structural modeling revealed that the VHH primarily recognizes the DE loop region of the VP3 capsid protein across the three serotypes, explaining its cross-serotype reactivity. Affinity chromatography using the VHH yielded infectious AAV particles, confirming its potential for downstream processing. This strategy provides a versatile platform for developing high-performance AAV affinity ligands and may be extended to other viral vector systems. Full article

The COVID-19 pandemic exposed the urgent need for innovative tools to strengthen pandemic preparedness and health defense, especially in low- and middle-income countries (LMICs). While vaccination has been the cornerstone of the defense strategy against many infectious agents, there is a critical gap in vaccine equity, ensuring it is accessible to all, especially among the most vulnerable populations. The conventional vaccine delivery platforms, through parenteral administration, face notable limitations, including reliance on trained personnel, sterile conditions, and cold chain logistics. The parenteral vaccines often fail to induce robust mucosal immunity, which is critical for preventing infections at mucosal surfaces, the primary entry point for many pathogens. Bacillus subtilis, a Gram-positive, spore-forming bacterium, has emerged as a promising platform for mucosal vaccine delivery owing to its Generally Recognized as Safe (GRAS) status. Its robust spores are highly resilient to harsh environmental conditions, which may eliminate the need for cold chain storage and further facilitate distribution in LMICs. This review explores the potential of B. subtilis as a next-generation vaccine delivery platform, focusing on its unique characteristics, mechanisms of action, and applications in addressing global health challenges. This review also examines existing research demonstrating the safety, immunogenicity, and efficacy of B. subtilis spore-based vaccines while identifying limitations and future directions for optimization as a scalable and adaptable solution for resilient health defense, particularly in LMICs. Full article

This paper explores the integration of computing and multimodal technologies into personal reading practices to enhance student engagement and knowledge assimilation in higher education. In response to a documented decline in voluntary academic reading, we investigated how technology-enhanced reading environments can re-engage students through interactive and personalized experiences. Central to this research is SmartRead, a proposed multimodal eReading platform that incorporates gamification, adaptive content delivery, and real-time feedback mechanisms. Drawing on empirical data collected from students at a higher education institution, we examined how features such as progress tracking, motivational rewards, and interactive comprehension aids influence reading behavior, engagement levels, and information retention. Results indicate that such multimodal interventions can significantly improve learner outcomes and user satisfaction. This paper contributes actionable insights into the design of innovative, accessible, and pedagogically sound digital reading tools and proposes a framework for future eReading technologies that align with multimodal interaction principles. Full article

Biomimetic nanocarriers, particularly membrane-based systems, have emerged as promising platforms for drug delivery. A thorough understanding of the molecular interactions that govern their assembly, stability, and cargo-loading efficiency is essential for optimizing their design and performance. Equally important are their interactions with biological components such as proteins, lipids, nucleotides, and cells, which significantly influence delivery efficacy. Among various techniques for characterizing these nanocarriers, isothermal titration calorimetry (ITC) has proven to be an invaluable tool to study their molecular interactions. ITC enables direct quantification of key thermodynamic parameters, such as binding affinity, stoichiometry, enthalpy, and entropy changes, without the need for molecular labeling or immobilization. This review highlights the application of ITC in the study of biomimetic nanocarriers, focusing on solid lipid nanoparticles, liposomes, extracellular vesicles, cell-derived vesicles and live cells. For each type of nanocarrier, the ITC applications in specific areas and the resulting information are discussed. For example, ITC was used to characterize drug interaction and protein adsorption for solid nanoparticles. In contrast, many aspects of liposomes were explored by ITC, including membrane solubilization and stabilization, peptide interactions, and macromolecule and protein adsorption. Overall, this review aims to provide a conceptual and practical framework for employing ITC in the investigation of biomimetic nanocarrier systems, facilitating their rational design and improved therapeutic performance. Furthermore, the discussion encourages further development of strategies to increase the application in cell-derived vesicles and live cells. Full article

The extensive use of submicron emulsion systems, particularly those stabilized by nonionic surfactants, with their proven effectiveness and safety profile, provides a reassuring foundation for our research. Consequently, we designed and engineered new submicron emulsion formulations stabilized with a biocompatible surfactant polyoxyethylated cocoamine, whose nonionic character is due to a high degree of polyoxyethylation. We chose oleic acid as the oil phase, a fatty acid known for its beneficial properties. This led to novel biocompatible nanoemulsions with high stability and cosurfactant-free microemulsions. The dynamic light scattering studies confirmed that both formulations have a nanometric size and low polydispersity index values. Moreover, transmission electron microscopy verified the nanodroplets’ morphological homogeneity and spherical shape. The resulting nanoplatforms can be applied to carry bioactive agents in the pharmaceutical and cosmetic fields. For this reason, we solubilized newly synthesized 5-dimethylamino-5′-nitro-2,2′-bithiophene as a model hydrophobic cargo for delivering poorly water-soluble compounds. This dye was chosen due to its strong solvatochromic behavior and suitability for micropolarity analysis via UV–Vis spectroscopy. We also present a simple method for rapid micropolarity screening to assess the type of nanodispersion via solvatochromic shift as an alternative procedure for evaluating of the oils used to fabricate nanoformulations for pharmaceutical and cosmetic purposes. Full article

Rapid access to defibrillators, blood products, and time-critical medicines can improve survival, yet urban congestion and fragmented infrastructure delay deliveries. We present and evaluate an end-to-end framework for beyond-visual-line-of-sight (BVLOS) UAV logistics in Essex (UK), integrating (I) strategic depot placement, (II) a hybrid obstacle-aware route planner, and (III) a time-window-aware (TWA) Mixed-Integer Linear Programming (MILP) scheduler coupled to a battery/temperature feasibility model. Four global planners—Ant Colony Optimisation (ACO), Genetic Algorithm (GA), Particle Swarm Optimisation (PSO), and Rapidly Exploring Random Tree* (RRT*)—are paired with lightweight local refiners, Simulated Annealing (SA) and Adaptive Large-Neighbourhood Search (ALNS). Benchmarks over 12 destinations used real Civil Aviation Authority no-fly zones and energy constraints. RRT*-based hybrids delivered the shortest mean paths: RRT* + SA and RRT* + ALNS tied for the best average length, while RRT* + SA also achieved the co-lowest runtime at $v=60\mathrm{km}{\mathrm{h}}^{-1}$. The TWA-MILP reached proven optimality in 0.11 s, showing that a minimum of seven UAVs are required to satisfy all 20–30 min delivery windows in a single wave; a rolling demand of one request every 15 min can be sustained with three UAVs if each sortie (including service/recharge) completes within 45 min. To validate against a state-of-the-art operations-research baseline, we also implemented a Vehicle Routing Problem with Time Windows (VRPTW) in Google OR-Tools, confirming that our hybrid planners generate competitive or shorter NFZ-aware routes in complex corridors. Digital-twin validation in AirborneSIM confirmed CAP 722-compliant, flyable trajectories under wind and sensor noise. By hybridising a fast, probabilistically complete sampler (RRT*) with a sub-second refiner (SA/ALNS) and embedding energy-aware scheduling, the framework offers an actionable blueprint for emergency medical UAV networks. Full article