Search Results (2,246)

Mesenchymal stromal cells derived from adipose tissue (ASCs) are widely used in regenerative medicine, requiring scalable expansion strategies that preserve both cellular function and biological quality. However, current bioprocess optimization approaches are primarily guided by proliferation and phenotypic stability, often overlooking genomic integrity as a critical attribute. In this study, we developed a stirred-tank bioreactor system for ASC expansion on microcarriers and applied a genotoxicity-informed optimization strategy by integrating growth kinetics, metabolic profiling, and DNA damage assessment across multiple operational conditions (B₁–B₅), including variations in dissolved oxygen, agitation, inoculum density, and medium renewal. Optimized culture conditions (B5) enabled high cell productivity within a reduced cultivation period (9 days), while maintaining high viability (>90%), mesenchymal immunophenotype, and differentiation capacity. Distinct metabolic profiles were associated with enhanced proliferation, with increased glycolytic activity observed under optimized conditions. Despite these favorable outcomes, genotoxic analyses revealed a progressive, time-dependent accumulation of DNA damage and increased micronucleus frequency during expansion. Notably, these alterations did not impair cell proliferation, phenotype, or differentiation potential, indicating that conventional optimization metrics may not fully capture underlying genomic changes. Collectively, our findings demonstrate that bioprocess optimization based solely on classical performance parameters may overlook relevant biological alterations. By incorporating genotoxic endpoints into the evaluation framework, this study provides a refined approach for assessing large-scale stem cell expansion and contributes to improving the robustness and reliability of biomanufacturing strategies for therapeutic applications. Full article

Large language models (LLMs) have demonstrated strong potential in medical knowledge applications; however, their reliability in knowledge-intensive medical reasoning—remains limited due to hallucination, inadequate domain grounding, and unstable inference behavior. These limitations are particularly pronounced in tasks of professional medical reasoning that require strict logical consistency and authoritative knowledge support. This study proposes a generative AI architecture that integrates RAG (Retrieval-Augmented Generation) with parameter-efficient supervised fine-tuning based on Low-Rank Adaptation (LoRA) to improve reasoning stability and diagnostic accuracy in complex medical domains. The architecture combines internalized domain reasoning learned through LoRA-based fine-tuning with external knowledge grounding enabled by a dynamic RAG mechanism, allowing the model to selectively retrieve domain-specific knowledge only when it is semantically relevant and evidence supported. To validate the proposed architecture, a large-scale real-world dataset comprising 11,476 multiple-choice questions from Taiwan’s national Traditional Chinese Medicine (TCM) licensing examinations (2005–2025) is constructed as a representative case study of knowledge-intensive medical reasoning. The experimental results show that the baseline LLM achieves an accuracy of 61.0%. Incorporating RAG improves accuracy to 89.0%, while combined LoRA-based fine-tuning and RAG architecture further increases accuracy to 90.1%, with reduced variance across repeated evaluations. Statistical analysis using McNemar’s test confirms that the performance improvements introduced by the retrieval mechanism are highly significant. The results demonstrate that integrating parameter-efficient fine-tuning with dynamically controlled retrieval is critical to balancing reasoning stability and knowledge enhancement in generative AI systems. Beyond the specific medical case study examined in this work, the proposed architecture offers a reproducible and extensible framework for developing reliable generative AI systems in other knowledge-intensive professional reasoning and educational domains. Full article

In this study, we investigated the interaction of a dapagliflozin-containing medicinal product (the commercial drug Forxiga^®) with human serum albumin (HSA) at different temperatures using steady-state fluorescence spectroscopy, competitive displacement assays, UV–Vis absorption spectroscopy, and thermodynamic analysis. Increasing concentrations of Forxiga induced a gradual, concentration-dependent quenching of the intrinsic fluorescence of HSA (${\lambda }_{\mathrm{ex}}=284$ nm; ${\lambda }_{\mathrm{em}\max }\approx 334$–339 nm), indicating perturbation of the microenvironment surrounding Trp-214 located in subdomain IIA. Stern–Volmer analysis showed that the quenching constants were temperature-dependent. Meanwhile, the high apparent bimolecular quenching constants suggested a predominantly static quenching mechanism associated with ground-state complex formation. By performing a modified Scatchard-type double-logarithmic analysis, we identified a primary binding site, particularly at lower temperatures. Van’t Hoff analysis revealed negative enthalpy and entropy changes. This indicates that the interaction was spontaneous and exothermic, mainly driven by hydrogen bonding and van der Waals forces. The competitive displacement assays confirmed preferential binding at Sudlow’s site I, in proximity to Trp-214. Additionally, the UV–Vis spectroscopy, supported by ligand-induced perturbation of aromatic residues, confirmed the absence of significant inner-filter effects. Differential scanning calorimetry suggested partial thermal stabilization of HSA upon ligand binding. This finding is consistent with the formation of a stabilized protein–ligand complex. These results suggest that Forxiga forms a relatively stable ground-state complex with HSA, primarily at Sudlow’s site I, and that the interaction is influenced by temperature-dependent conformational changes in the protein. Full article

Owing to its inherent electrical conductivity, reversible redox activity, and structural versatility, polypyrrole (PPy) has become an important material for advanced functional coatings. This review summarizes recent advances in PPy-based coatings, systematically exploring the correlation between fundamental material design and macroscopic multifunctional applications. First, the core structural characteristics of PPy and its primary fabrication strategies, including electrochemical deposition, chemical oxidative polymerization, solution processing, and hybrid composite engineering, are delineated. Subsequently, the role of PPy in surface protection is analyzed, with an emphasis on the synergistic mechanisms underlying corrosion mitigation, mechanical durability, and environmental barriers (e.g., anti-fouling and solar-driven desalination). In addition, the application expansion of PPy in emerging fields, such as electromagnetic interference (EMI) shielding, highly sensitive smart sensing, electroactive energy interfaces, and advanced biomedical electrodes, is summarized. Finally, current challenges—particularly the physicochemical trade-offs among conductivity, interfacial adhesion, and long-term stability—are discussed, and future development directions are prospected. By integrating green processing technologies and data-driven smart system integration, next-generation PPy coatings are expected to meet the demands of flexible electronics, sustainable energy, and precision medicine. Full article

Cathinone and its synthetic derivatives are among the most popular drugs worldwide. However, the literature provides data on the medicinal and cytotoxic potential of some of these compounds. These data are extremely limited due to the need to obtain additional permits for laboratory studies. Consequently, the therapeutic potential of cathinones may not have been fully explored. Furthermore, the literature provides data on the reduction or reversal of undesirable biological properties of drugs encapsulated in a bio-compatible carrier and administered through targeted therapy. The current study presents preliminary theoretical and experimental tests for further research on target cathinone–graphene–oxide complexes. A non-psychotropic cathinone model—o-fluorophenylacetic acid—was used. The NMR properties (chemical shifts, spin–spin coupling constants, and T₁ relaxation times) of graphene oxide–F-derivative complexes were measured at an acidic and neutral pH. To analyze the structure and stability of the possible complexes in different environments, molecular modelling was performed with simplified graphene oxide models using density functional theory. Experimental data were compared with theoretical values, and the most stable structures that may account for the observed spectral properties of the studied complexes were presented. The obtained data indicate a stronger tendency towards the formation and stabilization of GO-2-fluorophenylacetic acid complexes in a neutral environment. Full article

Background/Objectives: The convergence of traditional medicinal practices in Brazil’s vast biodiversity has fueled pharmaceutical interest in advancing plant-derived formulation. Copaiba (Copaifera spp.) and andiroba (Carapa guianensis) are central to both the economic landscape and healing traditions of the Amazon rainforest. Derivatives from these species have diverse applications, with their oils representing important raw materials for therapeutic use. However, the poor aqueous solubility of oils remains a major barrier to developing formulations with optimal bioavailability. Nanotechnology offers a strategic approach to address this limitation, as nanosystems improve stability, solubility, and biological performance. Methods: This narrative review compiles and analyzes contemporary literature on the chemical composition, physicochemical properties, and pharmacological activities of copaiba and andiroba oils, with emphasis on studies involving nanoformulations, aiming to overcome the solubility limitations of these oils. Results: Evidence from the literature indicates that nanoencapsulation enhances the anti-inflammatory, antimicrobial, and wound-healing activity of the oils’ main constituents, such as beta-caryophyllene and limonoids. However, inconsistencies in reported chemical composition and physicochemical properties across studies highlight the lack of standardized characterization and extraction methods, potentially hindering the development of reproducible nanosystems. Conclusions: Nanoencapsulation represents a promising strategy to improve the therapeutic potential of Amazonian oils. Nevertheless, further efforts are required to standardize methodologies and expand clinical studies to confirm the efficacy and safety of nanosystems derived from these natural products. Full article

Oxidative stress is a fundamental mechanism that impacts reproductive function by altering gamete quality, fertilisation, and the initial development of embryos. Excessive reactive oxygen species lead to the oxidation of polyunsaturated fatty acids in the cell membranes of sperm, oocytes, and adjacent somatic cells. F2-isoprostanes and isofurans are two of the most dependable indicators of oxidative lipid damage among the byproducts generated during free radical-mediated lipid oxidation. Both arise from the non-enzymatic peroxidation of arachidonic acid and provide a chemically stable depiction of in vivo oxidative processes. Reproductive studies indicate that elevated levels of F2-isoprostanes are associated with diminished sperm motility, compromised membrane stability, and an increased risk of DNA fragmentation in various forms of male infertility. Lipid peroxidation products have been detected in follicular fluid inside the female reproductive system, suggesting a relationship between oxidative imbalance, granulosa cell metabolism, and oocyte competency. Isofurans, which are more prevalent in the presence of elevated oxygen levels, may indicate oxidative stress in mitochondria and complications with cellular respiration. The current comprehension of lipid peroxidation indicators in infertility and assisted reproduction remains insufficient. This review aims to synthesise current information on isoprostanes and isofurans as reliable indicators of oxidative lipid damage in reproductive biology, highlighting their effects on gamete quality, mitochondrial dysfunction, and results in assisted reproduction. Our research seeks to clarify the biological importance of current experimental and clinical findings, highlighting their potential as clinically relevant biomarkers in reproductive medicine. Full article

Fraxinus chinensis Roxb. (Qinpi), a traditional Chinese medicinal plant, accumulates abundant coumarins that contribute to its anti-inflammatory and other bioactivities. However, the enzymatic basis for coumarin structural diversification in this species remains largely unexplored. Here, through transcriptome-wide identification of the 2-oxoglutarate-dependent dioxygenase (2OGD) family in F. chinensis, followed by phylogenetic analysis, heterologous expression, and in vitro enzyme assays, we identified FcDOH2, a member of the DOXC31 subfamily, which exhibits substrate-dependent bifunctionality, catalyzing the C6-O-demethylation of scopoletin (3) to esculetin (2) and the C8-hydroxylation of umbelliferone (1) to daphnetin (6). Using AlphaFold3-based structural modeling, molecular docking, and alanine scanning mutagenesis, we revealed that residues R155 and R221 are essential for both activities through stabilizing hydrogen bonds, whereas residue F312 acts as a functional switch, being critical for demethylation but negatively regulating hydroxylation. These findings uncover a rare bifunctional 2OGD with substrate-dependent catalytic plasticity, providing mechanistic insights into coumarin diversification in medicinal plants and a structural basis for future enzyme engineering. Full article

Sensors are an established driver of diagnostics and prevention in the medical field, including orthopaedics. Today, the subclass of ion-selective sensors (ISSs) is on the leading edge due to its advantages, enabled by technological advancements in manufacturing, such as miniaturization, precision, accuracy, specificity, a wide measuring scale, ease of use, flexible operating conditions, and measuring speed. While ISSs’ impact on environmental and health fields is already the subject of investigation, it still needs to be analysed specifically in orthopaedics, which is the aim of this Review. A PubMed and Scopus search was performed using the keywords “ion”, “sensor”, “electrodes”, “selective”, “musculoskeletal”, “implant”, “joint replacement”, and “orthopaedic”; after systematic screening, 44 studies were included in the synthesis. First, studies were classified based on the target ion. Only a few papers treated applications specifically in orthopaedics, confirming that ISSs are still largely an unexplored frontier here. However, all of the studies targeted ions with a role also in musculoskeletal pathophysiology, thus relative ISSs could have a potential impact on orthopaedic diagnosis and treatment. Then, when described by the papers, ISSs’ technological solutions were systematically evaluated. Finally, the main ISSs development targets for reaching orthopaedic clinical application were highlighted, including biocompatibility (e.g., implantability), long-term stability, calibration, and validation. Overcoming these challenges will enable ISSs to progress from laboratory prototypes to clinically viable tools, supporting the advancement of next-generation sensorised prostheses, fixation devices, and surgical instruments, and paving the way for predictive and personalised orthopaedic medicine. Full article

Background/Objectives: Orofacial myofunctional therapy (OMT) is a system of targeted neuromuscular exercises and behavioral retraining intended to optimize tongue, lip, jaw, and airway function during rest, breathing, swallowing, and sleep. Historically associated with tongue thrust and abnormal swallowing, OMT is now applied across an expanding range of clinical contexts, including sleep-disordered breathing (SDB), tongue-tie rehabilitation, orthodontic stability, and perioperative functional recovery. As its use has broadened, persistent questions have followed: what is myofunctional therapy, where did it originate, and how did a set of oral exercises evolve into an intervention increasingly integrated with airway health, sleep medicine, and surgical care? Methods: This article presents a narrative historical review with a perspective component, synthesizing foundational literature, interdisciplinary contributions, and selected contemporary evidence to examine the evolution of OMT from ancient functional practices to modern clinical science. It is written to trace recurring clinical observations, shifts in educational frameworks, and key inflection points that shaped how OMT has been taught and applied over time. Results: OMT did not emerge from randomized controlled trials or standardized protocols. It arose from repeated clinical encounters with patients with atypical craniofacial development, relapse of structural correction, persistent mouth breathing, and/or unresolved swallowing and speech dysfunction despite technically successful treatment. These patterns suggested that anatomy alone could not account for outcome variability. Over time, clinical attention expanded beyond isolated tongue function to include breathing patterns, posture, neuromuscular tone, and airway behavior. In the past two decades, controlled trials, cohort studies, and systematic reviews have supported selected applications of OMT, particularly in SDB and adjunctive airway care, while also revealing ongoing challenges related to training variability, terminology, scope of practice, and standardization. Conclusions: OMT has historically been described as a system of targeted neuromuscular and behavioral interventions aimed at modifying orofacial rest posture and function. Over time, the field has expanded beyond localized muscle retraining toward a broader functional framework that integrates airway physiology, craniofacial growth, sleep, and interdisciplinary rehabilitation. Full article

Peptide therapeutics have emerged as a versatile class of biomolecules bridging the gap between small-molecule drugs and large biologics. Advantages of such molecules include high target specificity, potent bioactivity and reduced off-target toxicity. Despite these, broader clinical translation remains constrained by inherent limitations like poor metabolic stability, rapid renal clearance, limited membrane permeability and scalable synthesis. This review aims to systematically integrate advances in peptide science across natural discovery, synthetic methodologies, structural engineering, and translational delivery systems, while identifying critical research gaps hindering clinical adoption. We highlight diverse natural sources of bioactive peptides, including plant- (lunasin), animal- (Val-Pro-Pro (VPP) and Ile-Pro-Pro (IPP)), microbial- (nisin and cyclosporine), marine- (dolastatins) and venom-derived (chlorotoxin and ω-conotoxin MVIIA (ziconotide)) agents. Advances in solid-phase peptide synthesis (SPPS), green chemistry, and catalytic strategies are discussed alongside emerging in silico approaches, including artificial intelligence-driven sequence design and molecular modeling. Structural modifications such as cyclization, hydrocarbon stapling, PEGylation, and lipidation are critically evaluated for their role in enhancing pharmacokinetic and pharmacodynamic properties. Furthermore, nanoformulation strategies, including self-assembling peptides and cell-penetrating systems, are examined for their potential to overcome biological barriers. Importantly, this review identifies key unresolved challenges, including the lack of predictive models for peptide delivery systems, safety concerns associated with long-term modifications, and limited in vivo validation of naturally derived peptides. Addressing these gaps through integrated computational and experimental approaches will be essential for advancing next-generation peptide therapeutics. Collectively, this work provides a comprehensive framework for the rational design and translation of peptide-based precision medicines. Full article

Three-dimensional (3D) bioprinting has rapidly evolved into a controlling platform for the fabrication of patient-specific biomedical implants, with growing importance in advanced drug delivery systems. Beyond structural tissue engineering, bioprinted constructs now function as programmable therapeutic depots capable of localized, sustained, and stimuli-responsive drug release. This review focuses on recent biomaterial design strategies that enable precise control over drug encapsulation, retention, and release kinetics within 3D bioprinted architectures. The physicochemical and mechanical properties of bioinks, including crosslinking density, porosity, degradation behavior, viscoelasticity, and swelling characteristics, directly influence drug loading efficiency and release dynamics under physiological conditions. The rational tuning of these parameters allows the development of constructs that provide spatially controlled and temporally regulated therapeutic delivery. Recent advances in predictive modeling, such as finite element modeling (FEM), data-driven machine learning approaches, and ML, have significantly improved the ability to correlate material composition, printing parameters, and structural geometry with drug diffusion and degradation-mediated release mechanisms. These tools facilitate the optimization of printing variables including extrusion pressure, nozzle diameter, and layer resolution to ensure structural fidelity while maintaining therapeutic functionality. Emerging strategies incorporating multi-material printing, gradient architectures, and stimuli-responsive biomaterials have expanded the potential of 3D bioprinting for combination therapies and personalized medicine. This review discusses key challenges in translating bioprinted drug delivery systems into clinical applications, including the standardization of drug release characterization methods, and long-term stability assessment. Full article

Progesterone (P4) exerts important vascular and immunomodulatory effects that influence platelet (PLT) activation and serotonin (5-HT) handling across mammalian species; nevertheless, its role in modulating PLT physiology during diestrus in mares remains poorly defined. This study hypothesized that physiological variations in luteal activity during diestrus are associated with changes in PLT activation and 5-HT-related parameters. The first objective was to determine whether changes in circulating P4 during diestrus are associated with alterations in PLT aggregation, circulating 5-HT, and PLT morphological indices in healthy mares; the second objective was to identify a diestrus day providing consistent physiological conditions for assessing PLT-related biomarkers. Twenty clinically healthy Spanish Purebred mares aged 4–9 years old were monitored. Blood samples were collected on days 5, 14, and 16 post-ovulation, with luteal status confirmed by ultrasonography. P4 concentrations were determined using a solid-phase I-125 radioimmunoassay (RIA), 5-HT concentrations were quantified using a competitive enzyme immunoassay, and PLT indices were measured using an ADVIA 2120i hematology analyzer. Data were compared using appropriate parametric or non-parametric tests after assessing distribution, and correlations were analyzed using rank-based correlation analysis, using Pearson or Spearman coefficients according to variable distribution. P4 concentrations were higher on days 14 and 16 compared with day 5 (p < 0.05), with no significant differences between days 14 and 16. Platelet aggregates (AGREG) showed the greatest variation, with significantly higher values on day 14 compared with day 5 (p < 0.05). In contrast, circulating 5-HT and all PLT morphological indices (PLT count, PCT, MPV, PLCR, PDW, PCDW, MPM, and PMDW) remained unchanged across diestrus. PLT aggregation showed a strong positive association with circulating P4 concentrations (r = 0.88, p < 0.05), whereas no meaningful correlations were observed between 5-HT and AGREG or between 5-HT and PLT morphological parameters. Internal correlations among PLT indices followed expected biological patterns, confirming the stability of structural PLT traits over short physiological intervals. These findings demonstrate that during diestrus, PLT activation—but not PLT morphology or circulating 5-HT—varies in parallel with P4 in mares. Day 14, corresponding to mid-diestrus, characterized by high luteal activity, represents an informative time point for assessing PLT activation and related biomarkers, providing a framework for standardizing sampling protocols for PLT-derived products in equine reproductive medicine. Full article

Mistreatment is a pervasive and normalized feature of medical culture. In medical residencies, it functions as a structural rite of passage that shapes professional socialization. While the prevalence of mistreatment is documented, there is a lack of qualitative research exploring its role as a mechanism of identity construction. The aim of this study was to understand the experiences of mistreatment among internal medicine residents in Medellín, Colombia, through the lens of ritual theory and symbolic violence. A particularistic ethnographic study was conducted with 12 residents selected via theoretical sampling. Data were collected through semi-structured interviews and a reflexive field journal. Rigor was ensured using investigator triangulation and analytical bracketing to manage researchers’ biases. The training process follows a three-stage rite. (1) Separation: Symbolic violence and social pressure to specialize frame general medicine as “mediocre,” turning admission into a “battlefield” where self-worth is tied to success. (2) Marginalization (Liminality): Residents endure systemic mistreatment, including sleep deprivation (3.5 h rest cycles), public ridicule (“pimping”), and physical/verbal abuse (e.g., being hit with stethoscopes or called “testicles/jerks”). This stage is governed by a “purificatory logic” where suffering is internalized as a meritocratic requirement. This leads to high morbidity, with clinical diagnoses of anxiety and depression. (3) Integration (Postliminality): Professional autonomy and financial stability act as a “redemption” that justifies past suffering. Mistreatment is not an isolated interpersonal issue but a structurally embedded ritual and a core element of the hidden curriculum. It reinforces toxic hierarchies and a “tyranny of merit” that obscures structural barriers. These findings offer analytically transferable insights for global medical education, calling for a deconstruction of ritualized violence to foster more humanistic training environments. Full article

Silver nanoparticles (AgNPs) have attracted substantial scientific interest in biomedical research owing to their unique physicochemical characteristics, broad-spectrum antimicrobial activity, plasmonic properties, and therapeutic versatility. Although conventional physicochemical synthesis methods enable controlled NPs fabrication, their dependence on hazardous reagents, elevated energy input, and environmentally detrimental processing conditions has stimulated the development of sustainable biogenic alternatives. Biological synthesis utilizing plants, microorganisms, fungi, algae, and purified biomolecules has emerged as an eco-friendly and bio-compatible strategy for AgNP fabrication, enabling simultaneous reduction, stabilization, and intrinsic biofunctionalization of NPs. However, traditional biogenic synthesis remains constrained by limited mechanistic understanding, poor batch reproducibility, inadequate control over physicochemical properties, and challenges in large-scale manufacturing. Recent advances in bioengineering have transformed this field through the integration of metabolic engineering, synthetic biology, microfluidic-assisted synthesis, artificial intelligence-guided process optimization, and continuous-flow biomanufacturing, collectively enabling precision fabrication of biogenic AgNPs with enhanced uniformity, scalability, and functional tunability. Furthermore, strategic surface engineering and functionalization have expanded the applicability of biogenic AgNPs across targeted anticancer therapy, antimicrobial intervention, wound healing, regenerative medicine, drug delivery, and theranostic imaging. Despite these advancements, critical challenges remain regarding nano–bio interactions, toxicological safety, regulatory compliance, and translational scalability. Unlike conventional reviews focused primarily on green synthesis approaches, this review critically highlights emerging bioengineering paradigms that enable programmable, scalable, and precision-controlled biogenic AgNP fabrication. This review comprehensively examines next-generation paradigms and strategies for AgNPs biosynthesis, elucidates the molecular mechanisms governing their formation, highlights emerging functionalization and biomedical application paradigms, and discusses current translational barriers. Forming biogenic composites of AgNPs and heteroatom doped carbon nanodots needs intense research in near future. Full article