Search Results (3,370)

Postoperative pain management (POPM) remains a major clinical challenge despite its vital importance in reducing surgical stress, enabling early mobilization, and limiting postoperative complications. Conventional analgesic strategies are often constrained by short drug half-lives, repeated dosing requirements, systemic adverse effects, and the risk of opioid-related toxicity or dependence. These limitations suggest that the mode of drug delivery, in addition to drug selection itself, is a critical determinant of therapeutic performance. In this context, electrospun fibrous meshes represent a promising platform for localized and sustained analgesic delivery. Their high surface-area-to-volume ratio, tuneable porosity, broad polymer compatibility, and capacity to incorporate single or multiple bioactive agents make them attractive candidates for postoperative applications. This review summarizes recent advances in electrospun meshes for POPM, with particular emphasis on fabrication strategies, polymer selection, drug incorporation approaches, drug-release behaviour, biological performance, and translational challenges. Full article

Background. Post-intubation cicatricial laryngeal stenosis (PICLS) represents one of the most severe long-term complications of pediatric airway management. By systematically analyzing clinical and procedural variables across different grades of PICLS, this study addresses a critical gap in pediatric airway research and provides clinically relevant descriptive data on stenosis severity. Materials and methods. A retrospective single-center case-series study was conducted and included pediatric patients (0–18 years) treated for PICLS at a tertiary referral pediatric otolaryngology center between 2016 and 2024. Spearman correlation and multiple regression analyses were used to evaluate possible associations between clinical factors and stenosis grade. Results. Among 172 children with PICLS, severe forms of stenosis (Grades 3–4) were observed in 37.2%, with predominant subglottic localization (85.3%). Age at primary intubation (p = 0.02) and the type of intubation (emergency/elective; p = 0.04) were the only variables significantly associated with stenosis severity in this cohort, whereas sex, reintubation, comorbidities, and delivery-related factors showed no significant associations. Mild stenosis (Grades 1–2) more frequently followed intubation for elective surgery and infections, whereas severe stenosis was more commonly associated with intubation due to central nervous system pathology and infections. Conclusions. Age at primary intubation and the type of intubation (emergency/elective) were associated with stenosis severity in this cohort. These findings should be interpreted in light of the retrospective case-series design and the absence of a control group, but they may contribute to improved clinical characterization of PICLS severity in children. Full article

Human neutrophil elastase (HNE) is a central mediator of neutrophil-driven inflammation. Yet, despite decades of research and drug development, therapies targeting HNE have not consistently translated into clear clinical benefits. We suggest that this translational gap partly arises from how HNE has traditionally been conceptualized, as a single enzyme to inhibit. In biological systems, however, HNE operates within a complex and tightly regulated network of proteases and inflammatory mediators. This network is spatially compartmentalized and strongly influenced by local redox conditions, making HNE activity highly context-dependent. From a systems perspective, HNE acts as an amplifier of inflammation. Its extracellular activity connects several pathological processes, including activation of innate immunity, extracellular matrix degradation, disruption of epithelial and endothelial barriers, and the transition toward chronic inflammation. In this review, we integrate insights from enzymology, systems biology, and clinical research to reassess the development of HNE inhibitors, ranging from endogenous antiproteases to more recent reversible synthetic compounds. Despite their chemical and pharmacological diversity, many of these strategies have encountered similar limitations. We therefore argue that future therapeutic approaches should move beyond the inhibition of HNE as an isolated target and instead aim to modulate the broader protease network, with particular attention to drug–target kinetics and precise delivery to disease-relevant microenvironments. Full article

The retromer is a highly conserved complex that mediates the trafficking of cargo proteins to the plasma membrane or the trans-Golgi network. In pathogenic microorganisms, retromer-dependent transport contributes to the delivery of virulence factors and promotes infection. The retromer consists of a sorting nexin dimer (SNX) and a cargo-selection complex (CSC), formed by Vps26, Vps35, and Vps29. In Entamoeba histolytica, the parasite that causes human amoebiasis, the retromer functions as a Rab7A GTPase effector and participates in phagocytosis and cytotoxicity. Although we previously characterized the roles of EhVps26 and EhVps35, the function of EhVps29 remained unclear. In this study, we analyzed the subcellular localization and functional role of EhVps29 in adhesion, phagocytosis, and cytopathic effect. EhVps29 localized to the plasma membrane, cytosol, vesicles, tubules, Golgi-like structures, MVBs and, for the first time, the nucleus. Immunofluorescence and Western blot assays demonstrated that EhVps29 modulates the localization of EhVps26, EhADH adhesin, and EhCP112 cysteine protease. Ehvps29 gene silencing and overexpression confirmed its involvement in virulence-associated processes. Immunoprecipitation and confocal microscopy results showed the interaction among EhVps29 and the ESCRT machinery members EhVps36 and EhADH. Our results indicate that EhVps29 is involved in parasite virulence and protein trafficking through recycling or degradation pathways. Full article

Diabetic wounds are a common and severe complication of diabetes mellitus, characterized by delayed healing due to persistent inflammation, impaired angiogenesis, and cellular dysfunction. Conventional therapeutic approaches remain limited in efficacy. In recent years, exosomes have attracted considerable attention in wound healing and regenerative medicine because of their crucial role in intercellular communication and tissue repair. However, rapid clearance of exosomes in vivo greatly limits their therapeutic efficacy. To address this critical limitation, we engineered a decellularized extracellular matrix (dECM)-based hydrogel system functionalized with exosomes derived from skin-derived precursor cells (SKPs). This biomimetic scaffold was designed to serve as a local exosome-delivery platform at the wound site, with the aim of improving exosome utilization and augmenting their regenerative effects. Comprehensive in vitro characterization demonstrated that the exosome-loaded composite hydrogels exhibited robust pro-angiogenic activity, as evidenced by enhanced endothelial cell proliferation, migration, and tube formation. Moreover, the hydrogels displayed significant antibacterial effects against wound-relevant pathogens and potent reactive oxygen species (ROS)-scavenging capacity, thereby mitigating oxidative damage. Notably, the composite hydrogels also promoted the phenotypic polarization of macrophages toward the pro-regenerative M2 phenotype. In parallel, in vivo studies using a streptozotocin-induced diabetic rat wound model confirmed that treatment with the composite hydrogels significantly accelerated wound closure rates compared to control groups. Histological and immunohistochemical analyses revealed enhanced angiogenesis, as evidenced by increased CD31-positive microvessel density, as well as improved collagen deposition, re-epithelialization, and an attenuated local inflammatory microenvironment characterized by reduced pro-inflammatory cytokine expression and elevated M2 macrophage infiltration. Collectively, the SKPs exosome-loaded dECM based composite hydrogels developed in this study represent a potential therapeutic strategy for the treatment of diabetic wounds. Full article

Background/Objectives: Goupi plaster (GP) is a traditional black plaster composed of a biphasic fibrous–oil matrix containing multiple bioactive compounds, and it has been widely used for the treatment of musculoskeletal disorders. Representative active compounds include sinomenine, osthole, cinnamaldehyde, and imperatorin, which exhibit anti-inflammatory and analgesic effects. However, due to its heterogeneous matrix structure and multi-component nature, the pharmaceutical delivery behavior of GP remains difficult to evaluate using conventional methods. Therefore, this study aimed to establish an integrated structure–release–permeation–pharmacokinetic evaluation framework to systematically characterize the transdermal delivery behavior of GP. Methods: GP was evaluated using multi-level analysis, including microstructural imaging (FESEM), in vitro release, ex vivo skin permeation, and in vivo dual-site microdialysis. Four representative bioactive compounds (sinomenine, osthole, cinnamaldehyde, and imperatorin) were selected as marker compounds. Release data were fitted to kinetic models, and structure–release relationships were examined using the Higuchi release constant (k_h). Skin-barrier alterations were assessed by attenuated total reflectance–Fourier transform infrared spectroscopy (ATR–FTIR) and differential scanning calorimetry (DSC). Local concentrations in subcutaneous (SC) and intra-articular (IA) compartments were measured by ultra-performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) to explore potential in vitro–in vivo correlation (IVIVC). Results: FESEM revealed a fibrous–oil network structure. GP exhibited sustained, diffusion-dominated release, with k_h = 0.9908–0.9977 and Korsmeyer–Peppas (K–P) release exponents (n) = 0.61–0.66, differing from active pharmaceutical ingredient (API) controls. Fiber area fraction and fiber length density showed negative correlations with k_h (r = −0.91 to −0.99); ex vivo permeation profiles varied among compounds, and ATR–FTIR and DSC analyses showed moderate changes in skin-barrier properties. Dual-site microdialysis demonstrated sustained local exposure, and a positive relationship was observed between in vitro release and in vivo concentrations. Conclusions: This study establishes an integrated structure–release–permeation–pharmacokinetic evaluation framework for traditional black plaster systems. The observed IVIVC is descriptive rather than predictive, reflecting a trend-level association under the current experimental conditions. These findings highlight the importance of integrating in vitro release, skin permeation, and local pharmacokinetics for understanding drug delivery behavior in complex transdermal matrix systems, and provide a methodological basis for quality consistency evaluation of traditional black plaster formulations. Full article

As natural nanoscale intercellular messengers, exosomes exhibit considerable potential in modulating inflammation, angiogenesis, immunoregulation, and tissue remodeling, making them attractive candidates for regenerative medicine. However, their clinical translation remains limited by rapid systemic clearance, nonspecific biodistribution, insufficient lesion retention, and functional attenuation in hostile pathological microenvironments. In this review, we propose that biomaterial engineering should evolve from providing passive exosome carriers to constructing active regulatory platforms capable of precise spatiotemporal control. We summarize engineering strategies along two complementary dimensions. In the temporal dimension, biomaterials can enable sustained, sequential, or microenvironment-responsive release to match the dynamic phases of tissue repair. In the spatial dimension, biomaterials can improve local retention, tissue anchoring, structural guidance, endogenous cell recruitment, and lesion-specific delivery. Using cutaneous wound healing, osteochondral regeneration, myocardial repair, and neural regeneration as representative examples, we further analyze these strategies through a “clinical challenge–engineering strategy–biological mechanism” framework, with particular attention to how engineered systems influence key signaling pathways such as PI3K/Akt, Wnt/β-catenin, NF-κB, and PTEN/PI3K/Akt/mTOR. We also discuss translational barriers, including exosome heterogeneity, safety concerns inherited from parental cells, large-scale GMP-compliant manufacturing, product standardization, storage stability, and regulatory classification of exosome–biomaterial hybrids. Finally, we highlight emerging directions, including multi-mechanism combinational systems, closed-loop responsive platforms, and artificial intelligence-assisted design for personalized exosome therapeutics. This review provides a design-oriented framework to accelerate the bench-to-bedside development of biomaterial-enabled precision exosome therapy. Full article

Cancer remains a major global health challenge, characterized by abnormal cell growth and metastasis. Current limitations of conventional therapies, particularly non-specific toxicity harming healthy cells, highlight the need for more targeted approaches. Nanotechnology offers a revolutionary solution, utilizing nanoparticles (NPs) for precise drug delivery to tumor sites while minimizing off-target effects. These nanometer-scale particles enable superior binding to cancer cell membranes, the tumor microenvironment, or nuclear receptors, facilitating significantly higher local concentrations of therapeutic agents. NPs, synthesized via physical, chemical, or biological methods, are categorized as organic (organic material-based) or inorganic (metallic particle-based). Key delivery mechanisms include the Enhanced Permeability and Retention (EPR) effect and Active Transport and Retention (ATR). This review specifically examines NP applications for the most prevalent cancers in the US (2025): breast, prostate, and lung. Gold and magnetic NPs show significant promise for early breast cancer detection. For lung cancer, polymeric NPs like PCL, PLA, and PLGA are effective carriers for peptides, proteins, and nucleic acids. BIND-014, a docetaxel-loaded NP formulation, represents an emerging strategy for prostate cancer. Clinically established examples include liposomal doxorubicin and albumin-bound paclitaxel. We comprehensively discuss the synthesis methods, delivery mechanisms, and the current landscape of NPs in research and clinical trials for these cancers. This analysis underscores the potential of nanotechnology to provide more effective and targeted therapeutic options for cancer patients in the future. A distinctive feature of this review is its comparative cancer-specific analysis of NP platforms in breast, prostate, and lung cancers. Unlike previous generalized reviews, this work integrates synthesis strategies, delivery mechanisms, translational challenges, and clinically relevant formulations to provide a bench-to-bedside perspective on the future of nanomedicine in oncology. Full article

Arginase 1 (ARG1) deficiency (ARG1-D) is a rare genetic disorder due to loss of ARG1, the final enzyme in the urea cycle. ARG1-D hepatocytes are impaired in converting arginine into urea, resulting in elevated peripheral arginine and ammonia, which leads to progressive neurological symptoms. Current therapeutic strategies mainly focus on managing plasma arginine and ammonia level, but long-term outcomes remain poor. While no approved treatment specific for ARG1-D is available in the United States, a recombinant protein-based enzyme replacement therapy is available in Europe. Recently, extracellular vesicles (EVs) are emerging as a powerful therapeutic vehicle. By using Capricor’s StealthX^TM platform, EVs were engineered to express human ARG1 on their surface or encapsulated within. Regardless of their localization on the EV membrane, nanograms of ARG1 carried by EVs were biologically active and able to convert arginine into urea as potent as micrograms of human recombinant ARG1 (rHuArg1). Furthermore, ARG1-encapsulating EVs (STX-Arg1-in) were able to deliver ARG1 intracellularly but not EVs carrying ARG1 on their surface or rHuArg1. STX-Arg1-in EVs were further evaluated in a series of in vivo studies, and the results showed that STX-Arg1-in EVs were non-toxic and able to restore arginase activities in the liver of Arg1^−/− mice, which led to a lowered plasma arginine concentration similar to that in wild-type mice. Most importantly, Arg1-in EVs expanded the lifespan of the lethal neonatal Arg1 deficiency mouse model. Taken together, our data suggested StealthX^TM-engineered STX-Arg1-in EVs have a better safety profile due to the extremely low dosage and have great potential as a novel enzyme replacement strategy for patients suffering from ARG1-D. Significance statement: Intracellular delivery of recombinant protein and improved llifespanare endpoints of successful enzyme replacement therapy for the treatment of ARG1-D. Using the StealthX platform, a fully functional ARG1 enzyme was engineered to be carried inside of the extracellular vesicles, which allowed for the intracellular delivery of ARG1 protein in vitro and in vivo, with an improvement of lifespan in a lethal neonatal mouse model of Arg1 deficiency. More importantly, no toxicity was observed, and efficacy was achieved with a low dose, setting the base for an improved therapeutic approach. Full article

Mastitis is a common disease in dairy cows, mainly caused by Staphylococcus aureus and Escherichia coli. Berberine (BBR) has antibacterial and anti-inflammatory potential, but its application is limited due to poor oral absorption and difficulty in reaching mammary tissue. To address this, this study developed a BBR-loaded composite ethosome hydrogel (BBR-CEH) to achieve targeted mammary delivery through local transdermal administration. The experimental results showed that BBR-CEH has good chemical stability and biosafety. Subsequently, a mouse mastitis model was established by intraductal injection of 50 µL of bacterial mixture (E. coli:S. aureus = 1:1, each at 1 × 10⁷ CFU/mL). The results showed that after BBR-CEH treatment, the mRNA expression of TNF-α (tumor necrosis factor-alpha), IL-6 (interleukin-6), and IL-1β (interleukin-1 beta) was significantly decreased, the mRNA expression of ZO-1 (zonula occludens-1), Occludin, and Claudin-4 was significantly increased, and Bax/Bcl-2 (Bcl-2-associated X protein/B-cell lymphoma 2) was significantly reduced (p < 0.01), indicating alleviation of mastitis by reducing inflammation, improving tight junctions, and inhibiting apoptosis. Finally, network pharmacology and in vivo experiments confirmed that its mechanism involves the NF-κB (nuclear factor kappa-B) and PI3K/Akt (phosphoinositide 3-kinase/protein kinase B) pathways. Thus, topical BBR-CEH may represent a promising new strategy for mastitis treatment. Full article

Background: Nanoporous anodic alumina (NAA) has emerged as a promising platform for localized drug delivery in biomedical implants owing to its tunable nanoscale pore structure and biocompatibility. However, achieving the desired pore characteristics currently relies on time-consuming trial-and-error adjustments of anodization parameters. Methods: We developed a comprehensive data-driven machine learning framework using a feed-forward artificial neural network (ANN) with three hidden layers (64-32-16 neurons) trained on 77 samples from a compiled dataset of 99 anodization experiments spanning 1995–2025. The model predicts the NAA pore diameter based on anodization conditions (electrolyte type, concentration, voltage, temperature, and time). Results: The ANN achieved R² = 0.803, root mean square error (RMSE) = 25.83 nm, and mean absolute error (MAE) = 17.05 nm on training data; however, 5-fold cross-validation revealed moderate generalization (CV R² = 0.471 ± 0.078). Multiple linear regression showed comparable training performance (R² = 0.804) but superior cross-validation (CV R² = 0.729 ± 0.083). Feature importance analysis identified anodization voltage (29.15% ANN importance) and electrolyte type (30.23%) as the most influential factors. Coupling ANN-predicted pore dimensions with Higuchi diffusion modeling demonstrated that the pore diameter increased from 50 to 100 nm, nearly doubling the initial release rates (8 to 11 h⁻¹) and reducing the time to 50% release from 39.1 to 20.7 h. Conclusions: This data-driven approach offers a powerful tool to reduce experimental iteration and accelerate the development of advanced drug-delivery implants by enabling the rational design of NAA pore structures for optimized drug loading and release kinetics. Full article

Methicillin-resistant Staphylococcus aureus (MRSA) is a major clinical problem due to its resistance, virulence, and biofilm formation, which diminish antibiotic efficacy. This review explores natural products and antimicrobial nanoparticles (NPs) as alternative and combined strategies for controlling MRSA. Natural compounds, such as plant metabolites, essential oils, antimicrobial peptides, and fungal products, act by disrupting membranes, interfering with cellular processes, and limiting biofilm formation. Antimicrobial NPs, especially metal and metal oxide materials, act through membrane damage, oxidative stress, and metal ion release, enabling activity against resistant bacteria and improving biofilm penetration. Combining natural products with NPs increases stability, delivery, and local activity, enhances antibacterial effects, and reduces effective doses. Green synthesis enables direct integration of bioactive compounds, while nano-delivery platforms optimize solubility and controlled release. Nanotechnology-based applications such as wound dressings, nanocarriers, and multifunctional platforms support localized and sustained treatment and promote tissue repair. Despite these advances, clinical use is still constrained by safety concerns, variability in NP properties, and the lack of standardized evaluation and regulatory frameworks. Overall, combining natural products with antimicrobial NPs offers a practical strategy to augment MRSA treatment, but further progress depends on consistent design, robust safety evaluation, and clinical translation. Full article

Ulcerative colitis (UC) is a chronic inflammatory disorder of the colon characterized by dysregulated mucosal immunity and progressive epithelial injury. Upadacitinib (UPA), a selective Janus kinase 1 (JAK1) inhibitor, has demonstrated clinical efficacy in UC, but its therapeutic application is often constrained by adverse effects arising from systemic drug exposure. This underscores the need for advanced, site-specific delivery systems that enhance local efficacy while minimizing systemic toxicity. Here, we developed a colon-targeted natural lipid nanoparticle formulation of UPA (UPA-nLNP) to improve therapeutic performance and safety. UPA-nLNP was prepared by thin-film hydration using digalactosyldiacylglycerol (DGDG), monogalactosyldiacylglycerol (MGDG), and phosphatidic acid (PA), mimicking the lipid composition of ginger-derived exosomal particles, and was characterized for particle size, surface charge, and encapsulation efficiency. The formulation exhibited excellent mucus-penetrating capability and was evaluated in a dextran sulfate sodium (DSS)-induced acute colitis model in C57BL/6 mice following oral administration (5 mg/kg). Pharmacokinetic analysis demonstrated increased colonic accumulation with reduced systemic exposure compared to free UPA. Treatment with UPA-nLNP improved body weight recovery, reduced disease biomarkers, and suppressed key proinflammatory cytokines in the colon, with no evidence of systemic toxicity. This innovative strategy holds strong potential to enhance the clinical utility of JAK1 inhibitors by providing a safer and more effective therapeutic approach for ulcerative colitis. Full article

Radiation therapy is a central component of the definitive and postoperative management for head and neck cancers (HNC), with intensity-modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT) now standard. Within these techniques, two principal boost strategies are used: simultaneous integrated boost (SIB) and sequential boost (SEQ). Although both are guideline-supported, they differ in planning logistics, treatment delivery, potential radiobiologic effects, adaptability to anatomic change, and potential toxicity profiles. In this narrative review, we summarize the key technical, dosimetric, and radiobiologic differences between SIB and SEQ and synthesize the available comparative clinical data, with a focus on their roles in contemporary dose de-escalation strategies. SIB allows for differential dosing within a single plan and potentially shorter overall treatment time but typically delivers higher biologically effective doses (BED) to elective nodal regions. SEQ requires two plans but offers greater flexibility for adaptive replanning, facilitates a lower BED to elective nodal volumes, and may allow for partial normal tissue recovery during the boost phase. Comparative studies, including retrospective series, randomized trials, and a meta-analysis, have not demonstrated consistent differences between SIB and SEQ in survival or local control, with mixed findings regarding toxicity. In the context of de-escalation, multiple prospective studies have successfully used SEQ to reduce elective nodal dose with low rates of elective nodal failure, while recent data suggest that SIB-based elective dose reduction may also be feasible in select settings. Overall, both SIB and SEQ are effective boost strategies in HNC radiotherapy. While practice is often driven by institutional workflow and clinician preference, emerging evidence suggests potential advantages of SEQ for elective nodal dose de-escalation. Further prospective studies are needed to better define the relative impacts of SIB and SEQ on toxicity and tumor control. Full article

Nanotheranostic platforms integrating diagnostic and therapeutic functions within a single system have attracted significant attention in precision medicine. However, conventional nanotheranostics based on systemic administration often suffer from off-target accumulation, limited retention at disease sites, and dose-limiting toxicity. To address these limitations, hydrogel-integrated nanotheranostic systems have emerged as a promising strategy for achieving localized diagnosis and therapy with improved spatial control and safety. This review provides a comprehensive overview of recent advances in hydrogel–nanomaterial nanotheranostic platforms, focusing on their design principles, diagnostic capabilities, and therapeutic applications. We discuss the complementary roles of hydrogels and nanomaterials, where hydrogels function as localized reservoirs and tissue interfaces, and nanomaterials provide imaging and therapeutic functionalities. Key integration strategies including physical encapsulation, chemical conjugation, and in situ nanoparticle formation are systematically compared. We further summarize localized diagnostic modalities such as real-time imaging and therapy monitoring, and highlight research-driven applications in cancer treatment, inflammation and infection management, and tissue regeneration. Finally, major translational challenges and future perspectives toward personalized, image-guided local theranostics are discussed. Overall, hydrogel-based nanotheranostic platforms represent a versatile approach for next-generation localized precision medicine. Full article