Search Results (12,774)

Intratumoral injections of macromolecules, such as biologics and immunotherapeutics, show promise in overcoming dose-limiting side effects associated with systemic injections and improve treatment efficacy. However, the retention of injectates in the tumor microenvironment is a major underappreciated challenge. High interstitial pressures and dense tumor architectures create shear forces that rapidly expel low-viscosity solutions post-injection. Injectable hydrogels may address these concerns by providing a viscoelastic delivery vehicle that shields loaded therapies from rapid expulsion from the tumor. A chitosan–glycerol hydrogel was thus developed and characterized with the goal of improving the injection retention of loaded therapeutics. The gelation parameters and mechanical properties of the hydrogel were explored to reveal a shear-thinning gel that is injectable through a 27-gauge needle. Biocompatibility studies demonstrated that the chitosan–glycerol hydrogel was nontoxic. Retention studies revealed significant improvements in the retention of model therapeutics when formulated with the chitosan–glycerol hydrogel compared to less-viscous solutions. Finally, release studies showed that there was a sustained release of model therapeutics of various molecular sizes from the hydrogel. Overall, the chitosan–glycerol hydrogel demonstrated injectability, enhanced retention, biocompatibility, and sustained release of macromolecules, indicating its potential for future clinical use in intratumoral macromolecule delivery. Full article

Background/Objectives: Targeting individuals with certain characteristics provides improved precision in many healthcare applications. An alert mechanism for COPD exacerbations has recently been validated. It has been argued that its efficacy improves considerably with stratification. This paper provides an in-depth analysis of the cough data of the stratified cohort to identify options for and the feasibility of improved precision in the alert mechanism for the intended patient group. Methods: The alert system was extended using a system complementary to the existing one to accommodate observed rapid changes in cough trends. The designed system was tested in a post hoc analysis of the data. The trend data were inspected to consider their meaningfulness for patients and caregivers. Results: While stratification was effective in reducing misses, the augmented alert system improved the sensitivity and number of early alerts for the acute exacerbation of COPD (AE-COPD). The combination of stratification and the augmented mechanism led to sensitivity of 86%, with a false alert rate in the order of 1.5 per year in the target group. The alert system is rule-based, operating on interpretable signals that may provide patients or their caregivers with better insights into the respiratory condition. Conclusions: The augmented alert system operating based on cough trends has the promise of increased precision in detecting AE-COPD in the target group. Since the design and testing of the augmented system were based on the same data, the system needs to be validated. Signals within the alert system are potentially useful for improved self-management in the target group. Full article

Introduction/Objective: Post-bariatric surgery patients require long-term, coordinated care to address complex nutritional, physiological, and behavioral challenges. Personalized smart nutrition, combining individualized dietary strategies with targeted monitoring, has emerged as a valuable direction for optimizing recovery and long-term outcomes. This article examines how traditional medical protocols can be enhanced by digital solutions in a multidisciplinary framework. Methods: The study analyzes current clinical practices, including personalized meal planning, physical rehabilitation, biochemical marker monitoring, and psychological counseling, as applied in post-bariatric care. These established approaches are then analyzed in relation to the NutriMonitCare system, a digital health system developed and tested in a laboratory environment. Used here as an illustrative example, the NutriMonitCare system demonstrates the potential of digital tools to support clinicians through real-time monitoring of dietary intake, activity levels, and physiological parameters. Results: Findings emphasize that medical protocols remain the cornerstone of post-surgical management, while digital tools may provide added value by enhancing data availability, supporting individualized decision making, and reinforcing patient adherence. Systems like the NutriMonitCare system could be integrated into interdisciplinary care models to refine nutrition-focused interventions and improve communication across care teams. However, their clinical utility remains theoretical at this stage and requires further validation. Conclusions: In conclusion, the integration of digital health tools with conventional post-operative care has the potential to advance personalized smart nutrition. Future research should focus on clinical evaluation, real-world testing, and ethical implementation of such technologies into established medical workflows to ensure both efficacy and patient safety. Full article

Demand Side Management (DSM) plays a crucial role in modern energy systems, enabling more efficient use of energy resources and contributing to the sustainability of the power grid. This study examines DSM strategies within a multi-environment context encompassing residential, commercial, and industrial sectors, with a focus on diverse appliance types that exhibit distinct operational characteristics and user preferences. Initially, a single-objective optimization approach using Genetic Algorithms (GAs) is employed to minimize the total energy cost under a real Time-of-Use (ToU) pricing scheme. This heuristic method allows for the effective scheduling of appliance operations while factoring in their unique characteristics such as power consumption, usage duration, and user-defined operational flexibility. This study extends the optimization problem to a multi-objective framework that incorporates the minimization of CO₂ emissions under a real annual energy mix while also accounting for user discomfort. The Non-dominated Sorting Genetic Algorithm II (NSGA-II) is utilized for this purpose, providing a Pareto-optimal set of solutions that balances these competing objectives. The inclusion of multiple objectives ensures a comprehensive assessment of DSM strategies, aiming to reduce environmental impact and enhance user satisfaction. Additionally, this study monitors the Peak-to-Average Ratio (PAR) to evaluate the impact of DSM strategies on load balancing and grid stability. It also analyzes the impact of considering different periods of the year with the associated ToU hourly schedule and CO₂ emissions hourly profile. A key innovation of this research is the integration of detailed, category-specific metrics that enable the disaggregation of costs, emissions, and user discomfort across residential, commercial, and industrial appliances. This granularity enables stakeholders to implement tailored strategies that align with specific operational goals and regulatory compliance. Also, the emphasis on a user discomfort indicator allows us to explore the flexibility available in such DSM mechanisms. The results demonstrate the effectiveness of the proposed multi-objective optimization approach in achieving significant cost savings that may reach 20% for industrial applications, while the order of magnitude of the trade-offs involved in terms of emissions reduction, improvement in discomfort, and PAR reduction is quantified for different frameworks. The outcomes not only underscore the efficacy of applying advanced optimization frameworks to real-world problems but also point to pathways for future research in smart energy management. This comprehensive analysis highlights the potential of advanced DSM techniques to enhance the sustainability and resilience of energy systems while also offering valuable policy implications. Full article

Poly(organo)phosphazenes (PPZs) are increasingly recognized as versatile biomaterials for drug delivery applications in nanomedicine. Their unique hybrid structure—featuring an inorganic backbone and highly tunable organic side chains—confers exceptional biocompatibility and adaptability. Through precise synthetic methodologies, PPZs can be engineered to exhibit a wide spectrum of functional properties, including the formation of multifunctional nanostructures tailored for specific therapeutic needs. These attributes enable PPZs to address several critical challenges associated with conventional drug delivery systems, such as poor pharmacokinetics and pharmacodynamics. By modulating solubility profiles, enhancing drug stability, enabling targeted delivery, and supporting controlled release, PPZs offer a robust platform for improving therapeutic efficacy and patient outcomes. This review explores the fundamental chemistry, biopharmaceutical characteristics, and biomedical applications of PPZs, particularly emphasizing their role in zero-dimensional nanotherapeutic systems, including various nanoparticle formulations. PPZ-based nanotherapeutics are further examined based on their drug-loading mechanisms, which include electrostatic complexation in polyelectrolytic systems, self-assembly in amphiphilic constructs, and covalent conjugation with active pharmaceutical agents. Together, these strategies underscore the potential of PPZs as a next-generation material for advanced drug delivery platforms. Full article

Androgenetic alopecia (AGA) is a common progressive hair loss disorder driven by elevated dihydrotestosterone (DHT) levels, leading to follicular miniaturization. This study investigated sulforaphane-rich broccoli sprout extract (BSE) as a potential oral therapy for AGA. BSE exhibited dose-dependent proliferative and migratory effects on keratinocytes, dermal fibroblasts, and dermal papilla cells, showing greater in vitro activity than sulforaphane (SFN) and minoxidil under the tested conditions, while maintaining low cytotoxicity. In a testosterone-induced AGA mouse model, oral BSE significantly accelerated hair regrowth, with 20 mg/kg achieving 99% recovery by day 15, alongside increased follicle length, density, and hair weight. Mechanistically, BSE upregulated hepatic and dermal DHT-metabolizing enzymes (Akr1c21, Dhrs9) and activated Wnt/β-catenin signaling in the skin, suggesting dual actions via androgen metabolism modulation and follicular regeneration. Pharmacokinetic analysis revealed prolonged SFN plasma exposure following BSE administration, and in silico docking showed strong binding affinities of key BSE constituents to Akr1c2 and β-catenin. No systemic toxicity was observed in liver histology. These findings indicate that BSE may serve as a safe, effective, and multitargeted natural therapy for AGA. Further clinical studies are needed to validate its efficacy in human populations. Full article

Elaeocarpus sylvestris (Lour.) Poir. var. ellipticus (Thunb.) H.Hara, an evergreen tree species native to Jeju Island, South Korea, has experienced a progressive decline associated with phytoplasma infection. This study aimed to evaluate the efficacy of oxytetracycline-based tree injection for suppressing phytoplasma and improving tree vitality. Two formulations—oxytetracycline hydrochloride (4.3%) and oxytetracycline calcium alkyltrimethyl ammonium (17%)—were administered to 40 infected individuals across two sites using a gravity-fed injection system. Treatment efficacy was evaluated based on chlorophyll content as an indicator of physiological recovery, while phytoplasma presence was assessed by PCR at 150 days after injection. The oxytetracycline hydrochloride group showed the highest suppression, with a 70% phytoplasma non-detection rate as determined by PCR analysis. Treated trees exhibited significantly higher chlorophyll content compared to untreated infected controls. These findings suggest that minimally invasive tree injection using oxytetracycline can provide temporary suppression of phytoplasma and support physiological recovery in E. sylvestris. Full article

Background/Objectives: Pulmonary vein isolation (PVI) via cryoballoon ablation (CBA) is a recommended therapeutic strategy for patients with symptomatic paroxysmal and persistent atrial fibrillation (AF) who are refractory to antiarrhythmic drugs. Although PVI has demonstrated efficacy in reducing AF recurrence and improving patients’ quality of life, its impact on respiratory function is not well understood, particularly in patients with comorbid conditions. The aim of the study was to search for functional predictors of the respiratory system in the process of evaluating the efficiency of clinical assessment of CBA in patients with AF. Methods: We conducted a prospective study on 42 patients with symptomatic AF who underwent CBA, assessing their respiratory function through spirometry before and 30 days after the procedure. Exclusion criteria included pre-existing lung disease and cardiac insufficiency. The impact of variables such as body mass index (BMI), coronary artery disease (CAD) and heart failure (HF) on spirometry parameters was analyzed using statistical tests. Results: No significant changes were observed in overall post-PVI spirometry parameters for the full cohort. However, post hoc analyses revealed a significant decline in ΔMEF₇₅ in patients with CAD and BMI ≥ 30 kg/m², whereas ΔFEV₁/FVCex was significantly increased in patients with HF, as well as in patients with ejection fraction (EF) < 50%. Conclusions: CBA for AF does not universally affect respiratory function in the short term, but specific subgroups, including patients with CAD and a higher BMI, may require post-procedure respiratory monitoring. In addition, PVI may improve lung function in patients with HF and reduced EF. Full article

Background: Pain is a complex phenomenon characterized by unpleasant experiences with profound heterogeneity influenced by biological, psychological, and social factors. According to the National Health Interview Survey, 50.2 million U.S. adults (20.5%) experience pain on most days, with the annual cost of prescription medication for pain reaching approximately USD 17.8 billion. Theranostic pain nanomedicine therefore emerges as an attractive analgesic strategy with the potential for increased efficacy, reduced side-effects, and treatment personalization. Theranostic nanomedicine combines drug delivery and diagnostic features, allowing for real-time monitoring of analgesic efficacy in vivo using molecular imaging. However, clinical translation of these nanomedicines are challenging due to complex manufacturing methodologies, lack of standardized quality control, and potentially high costs. Quality by Design (QbD) can navigate these challenges and lead to the development of an optimal pain nanomedicine. Our lab previously reported a macrophage-targeted perfluorocarbon nanoemulsion (PFC NE) that demonstrated analgesic efficacy across multiple rodent pain models in both sexes. Here, we report PFC-free, biphasic nanoemulsions formulated with a biocompatible and non-immunogenic plant-based coconut oil loaded with a COX-2 inhibitor and a clinical-grade, indocyanine green (ICG) near-infrared fluorescent (NIRF) dye for parenteral theranostic analgesic nanomedicine. Methods: Critical process parameters and material attributes were identified through the FMECA (Failure, Modes, Effects, and Criticality Analysis) method and optimized using a 3 × 2 full-factorial design of experiments. We investigated the impact of the oil-to-surfactant ratio (w/w) with three different surfactant systems on the colloidal properties of NE. Small-scale (100 mL) batches were manufactured using sonication and microfluidization, and the final formulation was scaled up to 500 mL with microfluidization. The colloidal stability of NE was assessed using dynamic light scattering (DLS) and drug quantification was conducted through reverse-phase HPLC. An in vitro drug release study was conducted using the dialysis bag method, accompanied by HPLC quantification. The formulation was further evaluated for cell viability, cellular uptake, and COX-2 inhibition in the RAW 264.7 macrophage cell line. Results: Nanoemulsion droplet size increased with a higher oil-to-surfactant ratio (w/w) but was no significant impact by the type of surfactant system used. Thermal cycling and serum stability studies confirmed NE colloidal stability upon exposure to high and low temperatures and biological fluids. We also demonstrated the necessity of a solubilizer for long-term fluorescence stability of ICG. The nanoemulsion showed no cellular toxicity and effectively inhibited PGE2 in activated macrophages. Conclusions: To our knowledge, this is the first instance of a celecoxib-loaded theranostic platform developed using a plant-derived hydrocarbon oil, applying the QbD approach that demonstrated COX-2 inhibition. Full article

Background/Objectives: Myelodysplastic syndrome (MDS) is a heterogeneous clonal hematopoietic disorder characterized by ineffective hematopoiesis and leukemic transformation risk. Current therapies show limited efficacy, with ~50% of patients failing hypomethylating agents. This review aims to synthesize recent discoveries through an integrated network model and examine translation into precision therapeutic approaches. Methods: We reviewed breakthrough discoveries from the past three years, analyzing single-cell multi-omics technologies, epitranscriptomics, stem cell architecture analysis, and precision medicine approaches. We examined cell-type-specific splicing aberrations, distinct stem cell architectures, epitranscriptomic modifications, and microenvironmental alterations in MDS pathogenesis. Results: Four interconnected mechanisms drive MDS: genetic alterations (splicing factor mutations), aberrant stem cell architecture (CMP-pattern vs. GMP-pattern), epitranscriptomic dysregulation involving pseudouridine-modified tRNA-derived fragments, and microenvironmental changes. Splicing aberrations show cell-type specificity, with SF3B1 mutations preferentially affecting erythroid lineages. Stem cell architectures predict therapeutic responses, with CMP-pattern MDS achieving superior venetoclax response rates (>70%) versus GMP-pattern MDS (<30%). Epitranscriptomic alterations provide independent prognostic information, while microenvironmental changes mediate treatment resistance. Conclusions: These advances represent a paradigm shift toward personalized MDS medicine, moving from single-biomarker to comprehensive molecular profiling guiding multi-target strategies. While challenges remain in standardizing molecular profiling and developing clinical decision algorithms, this systems-level understanding provides a foundation for precision oncology implementation and overcoming current therapeutic limitations. Full article

Background: Bimekizumab, secukinumab, and ixekizumab are IL-17-targeting biologics approved for the treatment of moderate-to-severe plaque psoriasis. While secukinumab and ixekizumab selectively inhibit IL-17A, bimekizumab targets both IL-17A and IL-17F, potentially providing greater anti-inflammatory efficacy. This study aimed to compare the real-world effectiveness, safety, and tolerability of these agents in a Polish dermatology center between 2019 and 2024. Methods: We conducted a retrospective analysis of 98 patients meeting at least one of the following criteria: PASI ≥ 10, BSA ≥ 10, DLQI ≥ 10, or involvement of special areas with inadequate response or contraindications to ≥2 systemic therapies. Patients with prior exposure only to IL-17 inhibitors were excluded. PASI, BSA, and DLQI scores were recorded at baseline, week 4, and week 12. Due to differences in dosing schedules, outcomes were aligned using standardized timepoints and exponential modeling of continuous response trajectories. Mixed-effects ANOVA was used to assess the influence of baseline factors (age, BMI, PsA status) on treatment outcomes. Adverse events were documented at each monthly follow-up visit. Results: Bimekizumab showed the greatest effect size for PASI reduction (Hedges’ g = 3.662), followed by secukinumab (2.813) and ixekizumab (1.986). Exponential modeling revealed a steeper response trajectory with bimekizumab (intercept = 0.289), suggesting a more rapid PASI improvement. The efficacy of bimekizumab was particularly notable in patients who were previously treated with IL-23 inhibitors. All three agents demonstrated favorable safety profiles, with no serious adverse events or discontinuations. The most frequent adverse events were mild and included upper respiratory tract infections and oral candidiasis. Conclusions: This real-world analysis confirmed that IL-17 inhibitors effectively improved PASI, BSA, and DLQI scores in moderate-to-severe psoriasis. Bimekizumab demonstrated the most rapid early improvements and a higher modeled likelihood of complete clearance, without significant differences at week 12. All agents were well tolerated, underscoring the need for further individualized, large-scale studies. Full article

Background: Charcot–Marie–Tooth (CMT) is a group of inherited diseases impairing the peripheral nervous system. CMT originates from genetic variants that affect proteins fundamental for the myelination of peripheral nerves and survival. Moreover, environmental and humoral factors can impact disease development and evolution. Currently, no therapy is available. Metabolomics is an emerging field of biomedical research that enables the development of novel biomarkers for neurodegenerative diseases by targeting metabolic pathways or metabolites. This study aimed to evaluate the metabolomics profile of CMT disease by comparing patients with healthy individuals. Methods: A total of 22 CMT patients (CMT) were included in this study and were demographically matched with 26 healthy individuals (C). Serum samples were analyzed through Nuclear Magnetic Resonance spectroscopy, and multivariate and univariate statistical analyses were subsequently applied. Results: A supervised model showed a clear separation (R²X = 0.3; R²Y = 0.7; Q² = 0.4; p-value = 0.0004) between the two classes of subjects, and nine metabolites were found to be significantly different (2-hydroxybutyrate, 3-hydroxybutyrate, 3-methyl-2-oxovalerate, choline, citrate, glutamate, isoleucine, lysine, and methyl succinate). The combined ROC curve showed an AUC of 0.94 (CI: 0.9–1). Additional altered metabolic pathways were also identified within the disease context. Conclusion: This study represents a promising starting point, demonstrating the efficacy of metabolomics in evaluating CMT patients and identifying novel potential disease biomarkers. Full article

Rheumatoid arthritis (RA) is a chronic systemic inflammatory disorder primarily targeting joints, leading to pain, swelling, and stiffness. RA results from the body’s own immune system attacking its own tissues. Currently, there are various treatments available for RA including disease-modifying antirheumatic drugs (DMARDs) and NSAIDs. Leflunomide (LEF) is a USFDA-approved synthetic DMARD which is being widely prescribed for the management of RA; however, it faces several challenges such as prolonged drug elimination, hepatotoxicity, and others. LEF exerts its therapeutic effects by inhibiting dihydroorotate dehydrogenase (DHODH), thereby suppressing pyrimidine synthesis and modulating immune responses. Emerging nanotechnology-based therapies help in encountering the current challenges faced in LEF delivery to RA patients. This review enlists the LEF’s pharmacokinetics, mechanism of action, and clinical efficacy in RA management. A comparative analysis with methotrexate, biologics, and other targeted therapies, highlighting its role in monotherapy and combination regimens and the safety concerns, including hepatotoxicity, gastrointestinal effects, and teratogenicity, is discussed alongside recommended monitoring strategies. Additionally, emerging trends in novel formulations and drug delivery approaches are explored to enhance efficacy and minimize adverse effects. Overall, LEF remains a perfect remedy for RA patients, specifically individuals contraindicated with drugs like methotrexate. The therapeutic applicability of LEF could be enhanced by developing more customized treatments and advanced drug delivery approaches. Full article

Background: A precise drug delivery system enables the optimization of treatments with minimal side effects if it can deliver medication only when activated by a specific light source. This study presents a controlled drug delivery system based on poly(lactic-co-glycolic acid) (PLGA) microparticles (MPs) designed for the sustained release of vancomycin hydrochloride. Methods: The MPs were co-loaded with indocyanine green (ICG), a near-infrared (NIR) responsive agent, and fabricated via the double emulsion method.They were characterized for stability, surface modification, biocompatibility, and antibacterial efficacy. Results: Dynamic light scattering and zeta potential analyses confirmed significant increases in particle size and surface charge reversal following chitosan coating. Scanning electron microscopy revealed uniform morphology in uncoated MPs (1–10 $\mathsf{\mu }$m) and irregular surfaces post-coating. Stability tests demonstrated drug retention for up to 180 days. Among formulations, PVI1 exhibited the highest yield (76.67 ± 1.3%) and encapsulation efficiency (56.2 ± 1.95%). NIR irradiation (808 nm) enhanced drug release kinetics, with formulation PVI4 achieving over 48.9% release, resulting in improved antibacterial activity. Chitosan-coated MPs (e.g., PVI4-C) effectively suppressed drug release without NIR light for up to 8 h, with cumulative release reaching only 10.89%. Without NIR light, bacterial colonies exceeded 1000 CFU; NIR-triggered release reduced them below 120 CFU. Drug release data fitted best with the zero-order and Korsmeyer–Peppas models, suggesting a combination of diffusion-controlled and constant-rate release behavior. Conclusions: These results demonstrate the promise of chitosan-coated NIR-responsive PLGA MPs for precise, on-demand antibiotic delivery and improved antibacterial performance. Full article

Endometriosis is a chronic inflammatory condition affecting approximately 10% of women of reproductive age, characterized by pelvic pain, dysmenorrhea, and infertility. Emerging evidence suggests a potential link between gut microbiota dysbiosis and endometriosis pathogenesis, mediated through hormonal regulation, immune modulation, and systemic inflammation. Dienogest (DNG) is widely used for endometriosis management, but its effects on gut microbiota remain underexplored. This study investigates the impact of DNG on gut microbial composition in endometriosis patients, aiming to elucidate its therapeutic mechanisms beyond hormonal modulation. DNG therapy led to a significant reduction in the Bacillota/Bacteroidota ratio (p = 0.0421), driven by decreased Staphylococcus spp. (p = 0.0244) and increased commensal bacteria such as Lactobacillus spp. and Collinsella aerofaciens (p = 0.049). Species richness and alpha diversity indices showed a non-significant upward trend. Notably, C. aerofaciens, a butyrate producer linked to gut barrier integrity, was detected twice as frequently during therapy. The study also observed reductions in facultative anaerobes like Enterococcus spp. and a trend toward higher titers of beneficial Bacteroidota. This study provides the first evidence that DNG therapy modulates gut microbiota in endometriosis patients, favoring a composition associated with anti-inflammatory and barrier-protective effects. The observed shifts—reduced opportunistic pathogens and increased symbionts—suggest a novel mechanism for DNG’s efficacy, potentially involving the microbial regulation of estrogen metabolism and immune responses. Full article