Search Results (4,587)

Traditional one size fits all pharmacotherapy often yields suboptimal clinical outcomes, preventable adverse drug reactions (ADRs), and significant drug waste, imposing substantial economic and ecological burdens on healthcare systems. This review evaluates the transformative potential of pharmacogenomics (PGx) testing, particularly cytochrome P450 (CYP) gene variants, as a foundation for an ecosystem-centric accountability framework for green pharmacy and links human metabolic variability to specific environmental outcomes. Personalized CYP profiling is shown to minimize the environmental release of unused drugs and potentially ecotoxic metabolites into aquatic ecosystems, in contrast to standard uniform drug use approaches. The limitations of ethnicity-based dosing models, which rely on population genetic variation, are examined in the context of increasing global genetic admixture. It is argued that individual genetic profiling, conceptualized as a PGx-Green Passport, provides a reliable safety standard that accounts for individual differences, thereby enhancing efficiency and well-being in a globalized society. By integrating clinical data, including real-world evidence on hospital utilization, with sustainability frameworks, this review demonstrates that PGx-guided therapy is not only a tool for clinical efficiency but also a fundamental requirement for systematically achieving environmentally sustainable healthcare. Full article

Background: Extracellular vesicles (EVs) released from skeletal muscle mediate metabolic communication via microRNAs (miRNAs). While both circadian rhythms and exercise influence metabolism, the joint modulation of the muscle-derived EV miRNA landscape by circadian rhythms and chronic exercise remains undefined, particularly under the metabolic stress of obesity. Methods: Employing a 2×2 factorial design (Phase: ZT3 vs. ZT15; Condition: sedentary vs. exercise; ZT, Zeitgeber Time), EV-enriched fractions were isolated from ex vivo quadriceps muscle (QUA) cultures of high-fat diet-fed mice following an 8-week treadmill training regimen using polymer-based precipitation, and comprehensive miRNA profiling was performed by small RNA sequencing. Results: Principal component analysis (PCA) revealed that circadian phase accounted for a greater proportion of global variance in EV miRNA profiles than exercise. Differential expression analysis identified miR-1a-3p and miR-1b-5p as upregulated across both composite phase and exercise contrasts; however, condition-specific analyses indicated that this signal was primarily driven by the sedentary-phase comparison (ZT15-sed vs. ZT3-sed), in which the miR-29 family was also prominently co-upregulated, rather than constituting independent phase and exercise effects; this phase-associated signature was absent in the corresponding exercise-condition comparison. Exploratory functional enrichment of experimentally validated targets revealed phase-preferential association with metabolic and iron–heme pathways, whereas exercise-associated miRNAs mapped to signaling, inflammatory, and transcription-related networks. Conclusions: Circadian phase was the dominant contributor to global variance in muscle-derived EV-enriched miRNA profiles in obesity, as reflected by the phase-associated separation along principal component 1 (PC1, 33.47% of total variance), with exercise introducing context-dependent adaptive modulation. This study provides a foundational basis for investigating the temporal regulation of muscle secretome dynamics under high-fat diet conditions, highlighting temporal specificity as a key dimension in EV-mediated exercise physiology research. Full article

The development of new materials that are inherently safe and sustainable has become a critical objective in the context of the green transition. This challenge is especially significant for plastics, which often contain complex mixtures of chemicals that may be released during various stages of their life cycle and that can pose risks to human health and the environment. Within this context, the Safe and Sustainable by Design (SSbD) framework was followed to support the design of an innovative epoxy–vitrimer composite that integrates non-releasable fire-retardant functionalities, aiming to produce safer, sustainable, and recyclable materials suitable for railway applications. A simple methodology was developed to identify release hotspots potentially affecting workers, consumers, and environmental species and organisms. Based on this, experimental simulations were conducted to evaluate the release of materials such as flame retardants, non-intentionally added substances, and microplastics at hotspots and to compare release profiles between a benchmark material and an SSbD alternative. The results demonstrate that the newly developed recyclable and less hazardous composites can also reduce material release under weathering and abrasion conditions. Full article

Background/Objectives: Although triple antibiotic paste is effective in managing infected primary teeth, its incomplete removability from tooth structure remains a major limitation, prompting the search for alternative drug-delivery systems. The aim of this study was to obtain a multi-antibiotic porous composite system for tailored drug delivery, to develop a formulation strategy, and to characterize the physicochemical properties and drug release. Methods: The developed composites consisted of a porous composite matrix (PCM; chitosan/bioactive filler) and two or three antibiotics (ciprofloxacin [CIP], metronidazole [MET], clindamycin [CLI]). Three methods of incorporating antibiotics were used: applying an antibiotic solution to the stabilized PCM; introducing an antibiotic solution into the polymer matrix; and introducing an antibiotic into the polymer matrix as nanoparticles. The physicochemical properties of the composites, including microstructure, compressive strength, and swelling, were assessed. The antibiotic release profile was assessed for up to 168 h. Results: The most advantageous method for introducing MET and CLI, in terms of release profile, was applying them to the PCM surface, whereas ciprofloxacin exhibited stable release when incorporated directly into the polymer matrix and entrapped during the stabilization process. The composites with nanoparticles, including MET or CIP, did not release any active substances during the experimental period. Conclusions: The results demonstrate that the developed formulation strategy enables the production of composites that rapidly release substantial amounts of the active substances within a short time frame and maintain their concentration for an extended period, which may be beneficial for the treatment of bacterial infections. Full article

The remarkable evolution of oncological therapies has dramatically improved cancer survival rates but has simultaneously introduced a significant burden of cardiovascular complications. Cardio-oncology has emerged as a critical multidisciplinary field focused on mitigating the “collateral damage” of life-saving anticancer treatments, ranging from traditional chemotherapeutics to novel immunotherapies. This review provides a comprehensive analysis of the pathophysiological mechanisms, clinical phenotypes, and evolving management strategies for cancer therapy-related cardiac dysfunction (CTRCD). An extensive synthesis of the current literature was conducted, focusing on the molecular pathways of cardiotoxicity, including Topoisomerase IIβ inhibition by anthracyclines, HER2 signaling disruption by targeted agents, and immune-mediated myocarditis triggered by checkpoint inhibitors (ICIs). Cardiotoxicity is increasingly recognized as a spectrum of phenotypes. Heart failure with reduced ejection fraction (HFrEF) remains a primary concern with cytotoxic agents, while heart failure with preserved ejection fraction (HFpEF) is emerging as a critical complication of radiation therapy and tyrosine kinase inhibitors (TKIs). The integration of advanced diagnostic tools—specifically Global Longitudinal Strain (GLS) and Cardiac Magnetic Resonance (CMR) mapping—has shifted the clinical focus toward subclinical detection. Furthermore, pivotal clinical trials such as PRADA and SUCCOUR have validated early pharmacological prophylaxis and strain-guided interventions. Emerging challenges, including the management of CAR-T cell-induced cytokine release syndrome and the specific cardiovascular needs of pediatric and geriatric populations, are also explored. The future of cardio-oncology lies in precision medicine, leveraging genomic profiling and artificial intelligence to identify high-risk individuals. A proactive, multidisciplinary approach is essential to ensure that the success of modern oncology is not compromised by irreversible cardiovascular morbidity. Full article

Thrombocytopenia is a frequent complication of patients presenting emergently across the world for a wide array of etiologies. From patients who develop thrombocytopenia due to invasive neoplastic disease affecting the bone marrow to patients who develop immune complications secondary to the formation of auto-antibody responses that drive patients’ platelet counts lower or even cause infection, these patients stress the clearest need for prompt tests to discern the more likely thrombocytopenic-inducing cause. It is in this setting that looking at other platelet variables easily obtainable from modern hematology analyzers has gained traction. One of the elements found in extended platelet profiles are immature platelets (youngest and newly released platelets), also known as reticulated platelets, which are readily measurable from a complete blood count. One of the advantages of obtaining these counts is that they represent the immediate response of the bone marrow to the thrombocytopenia and, depending on etiology inducing the thrombocytopenia, they also provide information on the marrow’s response to therapeutic approaches. It is in this context that this review will present information of how these relatively novel platelet parameters can be used in clinical practice and how they can be a rapid gauge of the body’s response to disease processes leading to platelet losses. Thrombocytopenias resulting from infection (sepsis, viremia), autoantibody formation (immune thrombocytopenia and immune-mediated thrombotic thrombocytopenic purpura), immune dysregulation (systemic lupus erythematosus), and iatrogenic (drug-induced) will be discussed and used to explain how these young platelet measurements can provide valuable clinical information. Full article

Lipid recovery efficiency from microalgal biomass is a critical factor in the commercial viability of biodiesel. Scenedesmus sp. presents a robust cell wall that necessitates the evaluation of specialised disruption techniques to enhance intracellular lipid release and subsequent fuel quality. This study investigated the efficacy of five cell disruption methods—microwaves, ultrasonication, lyophilisation, autoclaving, and electroporation—integrated with three distinct extraction procedures: cold extraction, Soxhlet extraction system, and microwave-assisted extraction. The qualitative and quantitative impacts of these treatments were assessed by analysing the fatty acid methyl ester (FAME) profiles via gas chromatography (GC) following transesterification. The highest total lipid yield (88.97%) was achieved through a combination of microwave disruption and Soxhlet extraction. However, the maximal proportion of methyl esters was obtained when ultrasonication was paired with microwave-assisted extraction (97.64%). Surface analysis using scanning electron microscopy (SEM) of samples subjected to different disruption procedures could support the conclusions. Similarly, when the microalgal biomass was lyophilised beforehand, microwave extraction increased the oleic acid content. These results indicate that the choice of disruption and extraction protocols significantly influences both lipid recovery rate and the proportion of fatty acids in the chemical composition of microalgae. Tailoring these processes is essential for optimising the fatty acid profile for high-quality biodiesel production. Full article

Organic farming is increasingly promoted as a sustainable alternative to conventional wheat production; however, its effects on grain quality and immunogenic potential remain insufficiently understood. This study evaluated the influence of the farming system (organic vs. conventional) on grain composition, technological quality traits, immunochemical reactivity, and immunogenic peptide profiles in 13 durum wheat varieties, including traditional and modern Tunisian varieties. Protein fraction content, amino acid composition, gluten-quality parameters, starch content, and immunochemical reactivity against anti-gliadin antibodies were determined. In addition, in vitro digestion followed by LC–MS/MS peptidomic analysis and epitope mapping was performed on representative ancient and modern varieties to investigate the release of celiac-disease-related immunogenic peptides after simulated gastrointestinal digestion. Protein content and quality traits were mainly genotype-dependent, with no consistent effect from the farming system across all varieties. Organic farming was associated with reduced starch accumulation (3.2–39.9% reduction) and lower immunochemical reactivity. Peptidomic analysis further revealed a reduced number and relative abundance (20.8–43.6% lower abundance) of immunogenic peptides in organically cultivated wheat compared with conventionally grown counterparts. This study highlights the significant interaction between the genotype and farming system, and provides a novel demonstration that organic management can reduce the abundance of celiac-disease-related immunogenic peptides, particularly in ancient varieties. Full article

Hydrogels are widely investigated as drug carriers for cancer therapy due to their ability to provide sustained release and reduce systemic side effects. In this study, MeBSA–PNIPAm hydrogels were developed as dual-temperature and pH-responsive systems for gastrointestinal delivery of 5-FU. MeBSA was successfully synthesized using glycidyl methacrylate and confirmed by FTIR and ¹H-NMR analyses. Hydrogels with varying MeBSA/NIPA ratios were prepared via redox polymerization. DSC results showed that increasing MeBSA content shifted the phase transition temperature of hydrogels, while TGA analysis revealed enhanced thermal stability with higher MeBSA incorporation. Temperature-dependent swelling experiments further demonstrated that the VPTT slightly shifted depending on the surrounding pH, indicating that the thermoresponsive behavior of the hybrid network is influenced by the pH-dependent charge state of the protein component. Swelling studies performed at 30, 37, and 40 °C and at pH 1.2 and 7.4 confirmed dual-responsive behavior. Drug loading efficiencies above 70% were achieved for all formulations. In vitro release studies at 37 °C demonstrated distinct composition-dependent release profiles. During the first 2 h, all hydrogels exhibited controlled and limited release without burst behavior under acidic conditions. Following the transition to pH 7.4, a composition-dependent increase in drug release was observed. GEL 4 achieved the fastest and highest cumulative release (91%), whereas GEL 1 provided the most sustained release over 72 h (32%). Kinetic analysis indicated diffusion-controlled release, best described by the Weibull and Korsmeyer–Peppas models. Cytocompatibility tests showed that fibroblast viability improved with increasing MeBSA content. Overall, protein-modulated dual-responsive hydrogels offer tunable and biocompatible platforms for stimuli-responsive gastrointestinal drug delivery applications. Full article

Paclitaxel is a first-line anticancer drug, but its low water solubility impedes bioavailability. The purpose of this study is to estalish a delivery strategy via carboxymethyl chitosan (CMCS)-encapsulated 6-deoxy-6-mercapto-β-cyclodextrins (dmβCDs)-modified concave cubic gold (CCGs) to achieve PTX release. CCGs were initially synthesized by the one-pot method and further modified by dmβCDs, the dmβCDs can effectively capture PTX molecules, followed by encapsulation with CMCS, and then prepare pH-responsive CMCS/dmβCDs/CCGs nanocarriers after lyophilization. Results indicated that desirable hexagonal CCGs with 50 ± 5 nm size can be obtained by adjusting H₂O₂ and HClO concentration. FT-IR, Raman and XRD spectra had confirmed dmβCDs successfully grafted to the surface of CCGs. Drug loading experiments demonstrated that the nanocarrier encapsulated PTX in amorphous powder or molecular form have a capacity of 55.05 µg/mL. Drug release experiments revealed PTX release from CMCS/dmβCDs/CCGs nanocarriers carrying a typical pH-responsive profile and indicating earlier release in an acidic environment than in a neutral or alkaline environment. The proposed method can be utilized to effectually achieve high-efficiency solubilization and targeted release inside tumor cells of PTX. Full article

The growing emphasis on sustainability, regional distinctiveness, and spontaneous fermentation in winemaking necessitates a more comprehensive understanding of local yeast populations and their functional mechanisms. In total, 115 indigenous yeast strains were examined for their enzymatic activities of potential vitivinicultural significance. The yeasts were screened for chitinase activity (biocontrol potential), glycosidase activity (terpene release), β-lyases (thiol release), and sulfite reductases (off-flavor formation), followed by quantitative analysis of the selected subsets. Yeasts were further evaluated for inhibition of fungal mycelial growth, VOC-mediated inhibition, and tolerance to commonly applied fungicides. Pre-field selection was refined using the niche overlap index and grapevine leaf disc assay. The results confirmed chitinolytic activity in four species; all strains exhibited hydrolase activities, with H. uvarum 116 displaying the highest cell-associated activity (6.32 U/g), while T. delbrueckii Sut94 showed the highest extracellular activity (1.36 U/g). β-glucosidase and β-lyase activities were widespread, whereas hydrogen sulfide production was infrequent. P. guilliermondii ZIM 624 showed the most comprehensive overall enzymatic profile, together with strong inhibition patterns. A field trial on Pinot cultivars (V. vinifera L.) further evaluated P. guilliermondii ZIM 624 within an integrated disease management approach, with responses being more pronounced in ‘Pinot noir’ than in ‘Pinot gris’. Full article

Background: The global rise in antimicrobial resistance (AMR) has created an urgent need for innovative antibacterial strategies and localized delivery systems. This study aimed to develop and characterize electrospun poly (vinyl alcohol) (PVA) nanofibers co-loaded with atorvastatin (ATR) and zinc oxide (ZnO) nanoparticles for use as a multifunctional topical platform for wound healing and infection control. Methods: ZnO nanoparticles were prepared via ball milling and characterized for size and zeta potential. Four PVA-based nanofiber formulations were fabricated using electrospinning: blank (F1), ZnO-loaded (F2), ATR-loaded (F3), and ATR/ZnO co-loaded (F4). The nanofibers were evaluated for morphology, thermal properties, crystallinity, and drug release. Antibacterial efficacy was tested against S. aureus, S. epidermidis, MRSA, and P. aeruginosa using broth microdilution and checkerboard assays. Biocompatibility and wound healing potential were assessed via MTT and fibroblast scratch assays on human foreskin fibroblasts (hFFs). Results: SEM imaging confirmed the production of uniform, bead-free nanofibers. ATR and ZnO nanoparticles were successfully incorporated in the nanofiber. The co-loaded formulation (F4) demonstrated a sustained release profile, releasing approximately 78.7% of ATR over 24 h. While all treatments showed limited activity against P. aeruginosa, the ATR/ZnO co-loaded nanofibers exhibited significantly enhanced antibacterial activity against Gram-positive strains, achieving the lowest MIC values (1.5–2.0 mg/mL). Synergy analysis confirmed an enhanced effect with ATR and ZnO against MRSA. Furthermore, F4 achieved the highest wound closure rate of 92.41% in 24 h while maintaining acceptable cytocompatibility. Conclusions: The integration of ATR and ZnO into PVA nanofibers provides an enhanced antibacterial effect consistent with the synergistic potential observed between free agents targeting Gram-positive wound pathogens. The platform’s ability to simultaneously inhibit bacterial growth and promote rapid fibroblast migration positions it as a promising localized therapeutic for managing infected wounds. Full article

This study aimed to develop a 100 mg immediate-release (IR) tablet containing dasatinib monohydrate, a tyrosine kinase inhibitor, using a Quality by Design (QbD) framework at laboratory scale. The development strategy focused on systematic identification and control of critical process parameters (CPPs) affecting tablet quality during wet granulation. Preformulation studies were conducted to evaluate key physicochemical properties of the active pharmaceutical ingredient (API), including solubility, particle size distribution, and crystallinity, which may influence dissolution behavior. A risk assessment approach based on preliminary hazard analysis (PHA) and failure mode and effects analysis (FMEA) was applied to identify high-risk process variables. Based on the risk assessment results, chopper speed during wet granulation and compression force during tableting were identified as critical process parameters. These factors were further investigated using a Design of Experiments (DoE) approach based on Define Custom Design (DCD) and response surface methodology (RSM) to evaluate their effects on critical quality attributes (CQAs), including dissolution performance, disintegration time, and tablet friability. Response surface analysis established a design space in which chopper speed ranged from approximately 2300–2500 rpm and compression force ranged from 11 to 13 kN, ensuring consistent tablet quality within the investigated operating range. The optimized process conditions produced tablets that satisfied predefined quality targets. Comparative dissolution studies demonstrated dissolution profiles comparable to the reference product across pH 1.2, 4.0, and 6.8 media, with similarity factor (f₂) values ranging from 51.18 to 85.23. The experimentally established design space demonstrated reproducible in vitro performance and physicochemical stability under accelerated storage conditions. Overall, this study demonstrates the practical application of a QbD-based development strategy integrating risk assessment and response surface optimization to improve process understanding and manufacturing robustness in wet granulation-based tablet production. Full article

In ground-source heat-pump (GSHP) systems equipped with a single U-tube borehole heat exchanger (BHE), the heat-carrier fluid in the return leg may release heat to the surrounding ground in the shallow part of the borehole. From a fluid energy balance perspective, this is an exothermic process; however, it is detrimental during heating operation: It lowers the effective source temperature available to the heat pump and therefore degrades the overall coefficient of performance (COP). This study proposes a measurement-driven procedure to determine the exothermic transition depth $z_{\uparrow }^{*}$ from temperature profiles recorded at multiple depths along the ascending (return) pipe. The borehole is discretized into axial segments and, assuming a constant mass flow rate, the linear heat-exchange rate is estimated from the segment-wise enthalpy change. Time integration yields the segment-wise net energy exchange $Q_{\uparrow ,i}$, which is then classified as exothermic or endothermic using an uncertainty-based threshold derived from the standard uncertainty of the temperature sensors. The exothermic transition depth $z_{\uparrow }^{*}$ is defined as the first statistically stable sign change in the integrated segment energy (from exothermic to endothermic) and is obtained by linear interpolation between adjacent segment centres. By summing the exothermic energy exchange and the corresponding average loss power, an equivalent change in source-side outlet temperature $∆T_{out}$ is estimated and interpreted in terms of COP impact using a Carnot-scaled surrogate model. For two representative operating conditions, $z_{\uparrow }^{*}$ was found at $31.17 \mathrm{m}$ and $24.01 \mathrm{m}$, respectively, while the average exothermic loss power remained approximately 0.48 kW. The estimated $∆T_{out}$ ranged from $0.52$ to $0.75 \mathrm{K}$, corresponding to a diagnostic COP improvement if this parasitic exothermic exchange could be mitigated. The present results should therefore be interpreted as a case study-based demonstration of the method on one instrumented borehole rather than as a universal quantitative prediction for other sites or borehole fields. Full article

The genus Erysimum (Brassicaceae) comprises more than 150 species distributed mainly across Europe, Central Asia, East Asia, the Middle East, North Africa and North America, many of which are traditionally used for treating cardiovascular, respiratory, and inflammatory disorders. Plants of this genus are rich in various groups of secondary metabolites, including cardenolides, glucosinolates and isothiocyanates released from them, sterols, phenolic compounds such as flavonoids and tannins, and other secondary metabolites. This review synthesizes its unique phytochemical profile, characterized by the coexistence of ancestral glucosinolates and independently evolved cardenolides. Over 100 cardenolide structures based on 15 aglycones have been reported from Erysimum, although the structural characterization of several compounds remains inconsistent or incomplete, with some glycosides still absent in major chemical databases. A variety of pharmacological activities have been documented for extracts and isolated constituents, including cardiotonic, anti-inflammatory, antioxidant, antimicrobial, and cytotoxic effects, supporting the therapeutic potential of the genus. Ecologically, the genus employs a two-tiered defense strategy where strophanthidin-based compounds deter butterfly oviposition and digitoxigenin-based compounds repel larval feeding. This review summarizes current knowledge on the taxonomy, distribution, phytochemical composition, and biological activities of Erysimum species, with a focus on cardenolide diversity, structural ambiguities, and research gaps that require further investigation. Full article