Search Results (835)

Chronic diseases, characterized by their high prevalence and protracted course, represent a paramount challenge to global public health, necessitating effective, evidence-based preventive strategies. While functional foods are widely recognized for their potential, a comprehensive synthesis elucidating their multitargeted mechanisms within a “food-medicine homology” framework and a clear trajectory from broad-spectrum health promotion to targeted intervention remains lacking. This review bridges this critical gap by systematically evaluating the scientific evidence and application potential of functional foods, with a specific focus on key bioactive compounds—β-glucan, omega-3 polyunsaturated fatty acids (PUFAs), dietary fiber, and catechins. We provide a critical analysis of how these components orchestrate synergistic effects at molecular, cellular, and systemic levels to counteract core pathological processes, including oxidative stress, chronic inflammation, metabolic dysregulation, and gut microbiota imbalance. Our unique contribution lies in integrating the ancient wisdom of food-medicine homology with modern multi-omics and evidence-based research, thereby proposing a refined nutritional intervention paradigm. The review offers critical insights into the convergent actions of these bioactives, their dose-response relationships substantiated by clinical meta-analyses, and the emerging role of gut microbiota-derived metabolites. Furthermore, this review also explores the emerging evidence for synergistic interactions among these key bioactives, proposing that their combined use may yield amplified and more network-based protective effects against chronic diseases through complementary mechanisms, aims to develop integrated prevention strategies targeting both cardiometabolic and neurodegenerative diseases. The integrated prevention strategies systematically connect mechanistic insights into bioactive compounds, evaluates the strength of clinical evidence, and examines the implications for regulatory standards and societal acceptance, thereby bridging the gap between basic science, clinical application, and public health policy. The “mechanism-to-evidence-to-regulation” framework in this review links molecular insights with clinical validation and regulatory implications, offering a holistic perspective rarely addressed in existing literature. Full article

Microfluidic cell culture systems and organ-on-a-chip platforms provide powerful tools for modeling physiological processes, disease progression, and drug responses under controlled microenvironmental conditions. These technologies rely on diverse cell culture methodologies, including 2D and 3D culture formats, spheroids, scaffold-based systems, hydrogels, and organoid models, to recapitulate tissue-level functions and generate rich, multiparametric datasets through high-resolution imaging, integrated sensors, and biochemical assays. The heterogeneity and volume of these data introduce substantial challenges in pre-processing, feature extraction, multimodal integration, and biological interpretation. Artificial intelligence (AI), particularly machine learning and deep learning, offers solutions to these analytical bottlenecks by enabling automated phenotyping, predictive modeling, and real-time control of microfluidic environments. Recent advances also highlight the importance of technical frameworks such as dimensionality reduction, explainable feature selection, spectral pre-processing, lightweight on-chip inference models, and privacy-preserving approaches that support robust and deployable AI–microfluidic workflows. AI-enabled microfluidic and organ-on-a-chip systems now span a broad application spectrum, including cancer biology, drug screening, toxicity testing, microbial and environmental monitoring, pathogen detection, angiogenesis studies, nerve-on-a-chip models, and exosome-based diagnostics. These platforms also hold increasing potential for precision medicine, where AI can support individualized therapeutic prediction using patient-derived cells and organoids. As the field moves toward more interpretable and autonomous systems, explainable AI will be essential for ensuring transparency, regulatory acceptance, and biological insight. Recent AI-enabled applications in cancer modeling, drug screening, etc., highlight how deep learning can enable precise detection of phenotypic shifts, classify therapeutic responses with high accuracy, and support closed-loop regulation of microfluidic environments. These studies demonstrate that AI can transform microfluidic systems from static culture platforms into adaptive, data-driven experimental tools capable of enhancing assay reproducibility, accelerating drug discovery, and supporting personalized therapeutic decision-making. This narrative review synthesizes current progress, technical challenges, and future opportunities at the intersection of AI, microfluidic cell culture platforms, and advanced organ-on-a-chip systems, highlighting their emerging role in precision health and next-generation biomedical research. Full article

Co-infections are increasingly recognized as drivers of disease in ornamental fish, yet their genomic underpinnings and zoonotic implications remain underexplored compared to farmed species. Leveraging a One Health perspective, we investigated an acute mortality event in koi carp and characterized a co-infection by opportunistic aquatic bacteria that are also implicated in human disease. We isolated Aeromonas veronii and Shewanella sp. from a moribund koi using culture, biochemical assays, and MALDI-TOF MS, then generated draft genomes and performed orthology (OrthoVenn3), pathway annotation (KEGG BlastKOALA/Mapper), secondary-metabolite mining (antiSMASH), and virulence/resistome screening (VFDB/CARD), complemented by antimicrobial susceptibility testing. Clinically, affected fish showed dropsy/ascites, scale loss, abnormal buoyancy, and reduced activity. Phylogenomics positioned A. veronii Koi-2 within the A. veronii complex near species thresholds (ANI ~96.1%; dDDH ~70.2%), while Shewanella sp. Koi-1 formed a distinct lineage below accepted cut-offs relative to S. seohaensis (ANI ~95.9%; dDDH ~67.6%). The virulome comprised 194 loci in A. veronii Koi-2 and 152 in Shewanella sp. Koi-1 is enriched for adhesion, secretion, iron uptake, and immune-evasion functions. Genotype–phenotype agreement was high for multidrug resistance: Shewanella sp. encoded OXA-436 and rsmA, matching β-lactam resistance and reduced fluoroquinolone/phenicol susceptibility, whereas A. veronii carried tet(A), OXA-1157, cphA3, sul1, and aadA3 consistent with tetracycline, β-lactam, sulfonamide, and aminoglycoside resistance profiles. In conclusion, genome-resolved diagnostics confirmed a mixed Aeromonas–Shewanella co-infection with broad virulence potential and convergent resistance mechanisms, supporting the routine use of genomics to distinguish single- versus mixed-agent disease and to guide dual-coverage, mechanism-aware therapy in ornamental fish medicine while informing zoonotic risk mitigation. Full article

Zinc oxide nanoparticles (ZnO NPs) are increasingly applied in medicine, cosmetics, and environmental technologies, yet their interactions with blood cells remain poorly understood, raising cross-species safety concerns. Using frog (nucleated) and human (anucleate) erythrocytes as comparative models, we show that cellular architecture fundamentally shapes responses to ZnO NPs exposure. Human erythrocytes exhibited a dose-dependent progression from membrane deformation to eryptosis and hemolysis, reflecting the pronounced vulnerability of anucleate cells. In contrast, frog erythrocytes sustained nuclear DNA damage while largely preserving membrane integrity, highlighting the protective or reparative role of the nucleus. Molecular docking revealed energetically favorable interactions of ZnO NPs with ERα-LBD and DNA (ΔG = −4.28 and −5.68 kcal/mol, respectively), while quantum chemical analyses indicated electron-accepting properties and a narrow HOMO–LUMO gap, suggesting efficient macromolecular interactions and intracellular ROS generation. Together, these findings demonstrate that the presence of a nucleus shifts the primary target of nanoparticle toxicity from membrane to genome, providing novel mechanistic insights. This comparative study offers a robust framework for understanding nanomaterial reactivity across taxa and informs One Health-oriented risk assessments. Full article

Paediatric formulations are pharmaceutical dosage forms specifically designed to meet the physiological, developmental, pharmacokinetic, and practical needs of patients from birth to adolescence. Developing safe, effective, and age-appropriate medicines for children remains a significant challenge due to their age-dependent variability in physiological development, pharmacokinetic profiles, and therapeutic needs. These differences, combined with practical barriers such as poor palatability, limited swallowability, inappropriate dosage form size, and instability, often lead to the modification of adult medicines—practices that can cause dosing inaccuracies, contamination risks, and reduced therapeutic efficacy. Three-dimensional printing has emerged as a promising solution to address these limitations by creating personalised paediatric dosage forms with adjustable strengths, multilayer structures for controlled release, and child-friendly shapes that may improve acceptability and adherence. This review offers an overview of the physiological, technological, and regulatory factors involved in developing 3D-printed paediatric medicines. The Critical Quality and Performance Attributes relevant to this field—including dose accuracy and flexibility, release kinetics, palatability, product dimensions, material choice, safety, stability, cost-effectiveness, production time, scalability, and reproducibility—are discussed in the article. Additionally, the review discusses the evolving Good Manufacturing Practice and regulatory landscape necessary to ensure the quality, safety, and consistency of 3D-printed medicinal products. Overall, these insights underline the transformative potential of 3D printing as a pathway towards safer, more effective, and truly personalised pharmacotherapy for paediatric patients. Full article

Background: Many biological drugs have a rival version produced from different cell lines by other manufacturers; these drugs are referred to as biosimilars. By providing accurate information, encouraging patient and medical community acceptance, and advocating for their appropriate usage, pharmacists can play a crucial role in supporting the uptake of biosimilar medicines. Aim: This study aimed to assess pharmacists’ knowledge and attitudes toward biosimilar medicines in the Aseer region in Saudi Arabia. Methods: The study employed a descriptive, cross-sectional design using an anonymous online self-administered questionnaire. The questionnaire was developed by adapting a previously validated instrument and consisted of three sections: demographic data, knowledge about biosimilars, and attitudes toward biosimilars. Two non-probability sampling approaches, i.e., convenience and snowball sampling, were using for data collection. Results: A total of 298 pharmacists participated in the current study. Overall, a total of 135 (45.3%) demonstrated good knowledge of biosimilar medicines, while 163 (54.7%) exhibited poor knowledge. The median knowledge score among the study participants was 5 (5–6). Only 26.2% of pharmacists in the current study correctly identified that biosimilars were not generics and not interchangeable with reference biologics. More experienced pharmacists and those working in industry-related sectors demonstrated greater knowledge of biosimilars (p < 0.05). Pharmacists in the current study demonstrated generally favorable attitudes toward biosimilar medicines. Conclusions: The current study revealed knowledge gaps regarding biosimilar medicines among pharmacists. Targeted educational initiatives, continuing professional development opportunities, and enhanced curricular content could be implemented to address these gaps. Full article

Plants have been used in medicine for centuries to treat various diseases, with alcohol and ethanol being known as universal solvents for the extraction of medicinal plant substances. This article sheds light on Artemisia absinthium (wormwood) and absinthe usage in the history of medicine. The invention of absinthe in Switzerland in 1797 made it an integral part of everyday life and the harmful effects of the massive consumption of this product were labelled absinthism. The medicinal properties of wormwood and absinthe are explored from the earliest records of the use of wormwood from the Ebers Papyrus (copies of which date back to 1550 BC) to the military consumption of absinthe during the French invasion of Algiers in 1830. As widely accepted, A. absinthium has both anthelmintic and antiprotozoal properties. In addition, modern medicine has demonstrated antibacterial, antifungal and antibiofilm properties of the plant extracts. In order to fully utilise the therapeutic potential of A. absinthium, advances in pharmaceutical technology are essential. One promising solution could lie in nanotechnological delivery systems. In our opinion absinthe is another impressive example of how tonics containing various herbal substances were used in the history of medicine to manage infections before their efficacy was later proven in vitro and in vivo. Full article

Background: Dementia is a chronic, multifactorial syndrome with a high incidence and prevalence worldwide. The clinical assessment of these patients is challenging, imposing several barriers related to the system, the healthcare professional and the patient. While numerous assessment tools exist for dementia, few are specifically validated or widely used in palliative care. This study evaluates the relevance of using the Integrated Palliative Outcome Scale for Dementia (IPOS-Dem) in Portugal. The primary objective is to synthesize evidence on the implementation and clinical performance of IPOS-Dem in people with dementia receiving palliative care—including feasibility, acceptability, validity, reliability, and clinical applicability—while the secondary objective is to assess the instrument’s relevance and potential for cultural/linguistic adaptation to context. Methods: A systematic review of the literature was carried out, with research in evidence-based medicine databases on the use of the Integrated Palliative Outcome Scale for Dementia (IPOS-Dem) in palliative care, using the terms “dementia”, “alzheimer”, “lewy body”, “cognitive impair”, “outcome”, “IPOS-Dem”, “patient outcome assessment”, “outcome assessment”, “scale”, “palliative care”, and “palliative outcome scale”. Results: The IPOS-Dem was considered to be a useful tool for monitoring patients with dementia while receiving palliative care, allowing for a comprehensive and systematic evaluation of symptoms, as well as involving family members in the care process. It facilitates the identification of previously unknown symptoms and issues, particularly emotional and social concerns. Its use led to an improvement in symptom control and greater family involvement in care. The reduction in missing response rates and the time required to complete the scale with repeated use indicated good adaptation to the scale’s implementation. Difficulties were reported in assessing patients with communication impairments. Some staff also highlighted the need for training in using the scale. The Swiss Easy-Read IPOS-Dem showed significant variation in scores between evaluators, which raises concerns about the reliability and consistency of the scale, indicating that the tool requires further validation. Digital models, although they may present some inconveniences, were suggested as a potential improvement in acceptability. Conclusions: Our review suggests that IPOS-Dem provides initial evidence of feasibility, acceptability, and potential clinical usefulness in dementia palliative care, making its implementation beneficial for the Portuguese population. Translation and adaptation to the Portuguese population and culture will be necessary, but the scale is promising, and we recommend its national use. Full article

Knee osteoarthritis (KOA), a common degenerative joint disease, affects a large patient population and poses significant challenges in early diagnosis and rehabilitation. Achieving precise assessment of knee function and efficient home-based intelligent rehabilitation is crucial for alleviating pain, slowing disease progression, and improving patients’ quality of life. This study proposes a smart wearable knee function assessment based on multimodal physiological signals and a rehabilitation system. The system integrates surface electromyography (sEMG), pressure sensors, and an inertial measurement unit (IMU) to synchronously capture gait, posture, and muscle activity. It quantifies knee function by extracting gait and EMG features. Additionally, a wearable massage device driven by airbags was designed and implemented to simulate the traditional Chinese medicine “seated knee-adjustment method” and deliver precise intelligent rehabilitation interventions. Experimental results validated the system’s accuracy in functional assessment and reliability in rehabilitation assistance. The average relative error in gait feature extraction was below 8%, while the massage head displacement error remained within clinically acceptable ranges. By integrating multimodal sensing technology with intelligent rehabilitation devices, this system offers KOA patients a convenient, efficient, and sustainable home-based rehabilitation solution with strong clinical application potential and promotional value. Full article

Background/Objectives: The Developing and Evaluating a Machine Learning Opioid Prediction & Risk-Stratification E-Platform (DEMONSTRATE) trial aims to assess the usability, acceptability, feasibility, and effectiveness of implementing a machine learning (ML)-based clinical decision support (CDS) tool—the Overdose Prevention Alert—which predicts a patient’s risk of opioid overdose within three months. Methods: This single-arm study uses a pre–post implementation design with mixed-methods evaluation in 13 University of Florida Health, Gainesville, internal medicine and family medicine clinics. Eligible patients are aged ≥18 years, received an opioid prescription within the year prior to their upcoming primary care visit, are not receiving hospice care, do not have a malignant cancer diagnosis, and are identified by the ML algorithm as high risk for overdose. The Overdose Prevention Alert triggers when a primary care provider (PCP) signs an opioid order in electronic health records. We will evaluate effectiveness by comparing pre- and post-implementation outcomes using a composite patient-level measure defined by the presence of any of the following 6 favorable indicators: (1) evidence of naloxone access; (2) absence of opioid overdose diagnoses and naloxone administration; (3) absence of emergency department (ED) visits or hospitalizations due to opioid overdose or opioid use disorder (OUD); (4) absence of overlapping opioid and benzodiazepine use within a 7-day window; (5) absence of opioid use ≥50 morphine milligram equivalent daily average; (6) receipt of referrals to non-pharmacological pain management. Additional quantitative metrics will include alert penetration, usage patterns, and clinical actions taken. Usability and acceptability will be assessed using a 12-item questionnaire for PCPs and semi-structured interviews. Expected Results: The trial will provide insights into real-world ML-driven CDS implementation and inform future strategies to reduce opioid-related harm. Full article

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies. An unmet need exists for reliable biomarkers and in vitro models capable of predicting patient drug response to advance personalized medicine. Traditional models fail to represent the tumor’s complexity and the role of the stromal environment in chemoresistance. Patient-derived organoids (PDOs) overcome these limitations, enabling multi-omics profiling and reliable drug testing for functional precision medicine. This review provides a comprehensive overview of PDAC PDO research, emphasizing the following major areas: (i) the genetic and phenotypic fidelity of PDOs, (ii) their predictive value for drug response and chemoresistance, (iii) the integration of the extracellular matrix and tumor microenvironment (TME) components, and (iv) emerging technologies. Studies confirm that PDOs faithfully represent the primary tumor’s specific genetic features and retain intratumoral heterogeneity. PDO-based platforms have demonstrated a strong correlation between in vitro drug sensitivity and in vivo efficacy in xenograft models, validating their utility for identifying drug candidates, repurposing existing drugs, and determining effective combinations. Efforts are ongoing to integrate crucial TME components, like cancer-associated fibroblasts, using innovative co-culture platforms such as fused PDOs and InterOMaX, to better model desmoplasia and chemoresistance mechanisms. Furthermore, PDO technology is converging with microphysiological systems and artificial intelligence tools to facilitate high-throughput drug screening and dynamic, real-time monitoring of therapeutic effects. The integration of PDOs into biobanks and advanced screening platforms holds the potential to accelerate drug discovery and improve therapeutic outcomes for PDAC patients, if challenges related to protocol standardization and regulatory acceptance are addressed. Full article

Community-level overdose prevention interventions often require collaboration among organizations from various sectors including emergency medicine, criminal justice, harm reduction, and drug treatment organizations, yet little is known about ways to foster interorganizational collaboration among organizations with very different missions and in different socio-political contexts. This paper presents results from interviews with key informants involved in overdose prevention coalitions in two counties in Wisconsin (n = 45). Key informants were purposively selected from 31 different organizations in sectors including harm reduction, drug treatment, emergency medicine, and law enforcement. Interviews asked participants to describe the overdose crisis in their communities and the work they do, including any partnerships or coalitions formed with other organizations. We conducted thematic analysis using inductive and deductive coding. Participants’ experiences illuminate strategies and actions that facilitated coalitions’ work (interorganizational processes) and changed the context in which they worked to be more accepting of harm reduction efforts and less stigmatizing and punitive toward people who use opioids (PWUO). These included getting the word out in community-facing events to educate the public and destigmatize harm reduction, working with representatives across the CoC in various sectors, and actively working with them to create shared missions. Key people acted as bridges while others had the power to convene multiple agencies to a common cause. Overdose Fatality Reviews (OFRs) were found to be particularly helpful in identifying gaps in the current Opioid CoC and developing programs in collaboration with other organizations to address them. Organizational empowerment offers a useful framework for understanding how to facilitate IOC at the intra- (e.g., community education to reduce stigma, inter- (bridging roles by key actors), and extra-organizational levels (e.g., policy changes supporting naloxone access). These strategies can be used by coalition members and tested in future community-level overdose responses. Full article

Background: Asarum heterotropoides, a prominent medicinal plant in China, is well known for producing an abundance of monoterpenes and sesquiterpenes, which constitute the primary components of its essential oil and serve as the principal active compounds of the species. However, the biosynthetic pathways for these terpenoids remain largely unelucidated. Methods: Gas chromatography–mass spectrometry analysis, in vitro enzyme assay, subcellular localization experiment and molecular docking were used to characterize the function of terpene synthase from A. heterotropoides. Results: In this study, we isolated and characterized two monoterpene synthases and one sesquiterpene synthase from A. heterotropoides. These enzymes exhibit promiscuous activities, accepting geranyl pyrophosphate and farnesyl pyrophosphate as substrates to yield a variety of monoterpene and sesquiterpene products in in vitro enzymatic assays. All three enzymes possess a conserved RRx8W motif, a hallmark typically associated with TPS-b and TPS-d monoterpene synthases involved in cyclic monoterpene formation. However, these two monoterpene synthases yield linear instead of cyclic products. The sesquiterpene synthase (AhTPS3) is a second example of TPS-a terpene synthase harboring such motif. Conclusions: Our findings significantly expand our understanding of terpene biosynthesis, especially the role of RRx8W motif. Full article

Coix seed, a traditional medicinal and edible crop, is susceptible to mycotoxin contamination posing potential health risks, yet systematic risk assessments for its dual dietary and medicinal pathways remain limited. Fifty batches were collected from five major production regions in China. UPLC-MS/MS was used to quantify eight mycotoxins in raw materials and decoctions. A Monte Carlo simulation model assessed long-term (20-year) health risks via both pathways, and acceptable daily intake (ADI) levels were derived using a combined margin of exposure (MOE) threshold of 10,000. Results indicated that mycotoxins were present in 94% of samples. Zearalenone (ZEN) was the most frequent, with an occurrence of 82% and concentrations of 52.16~1804.43 μg/kg. Dietary exposure indicated potential risks for ZEN (MOE = 259), aflatoxin B1 (AFB1, MOE = 666), and AFB2 (MOE = 8040). Six mycotoxins transferred to decoctions at rates of 0.70~19.73%, with long-term medicinal use indicating potential ZEN-related risk (MOE = 4880). Multi-mycotoxin co-exposure assessment revealed elevated dietary risk (combined MOE = 181), whereas medicinal exposure within a standard 3-month treatment course remained within acceptable limits. Safety intake thresholds are proposed: ≤30 g/day for ≤130 days (dietary) and ≤30 g/day for ≤2000 days (medicinal). This study establishes a risk assessment framework applicable to herbal materials with both dietary and medicinal applications. Full article