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Background/Objectives: Wound healing proceeds in a timely and sequential manner through four well-defined phases: hemostasis, inflammation, proliferation, and remodeling. To explore the therapeutic efficacy and underlying mechanism of a novel monoacylglycerol lipase (MAGL) inhibitor (designated as MAGL11), a diabetic mouse model of skin wounds was established. Methods: Wound healing progression was assessed via gross observation, while histological analyses (including HE staining and Masson staining) were conducted to evaluate tissue repair. Additionally, proteomic analysis and in vitro experiments were employed to validate the therapeutic effects and clarify the molecular mechanism of MAGL11. Results: In vivo studies revealed that treatment with MAGL11 significantly accelerated wound closure in diabetic mice. Compared with the control group, MAGL11-treated wounds exhibited notably increased granulation tissue formation and collagen deposition, which was accompanied by a distinct anti-inflammatory effect. Results from proteomic profiling and in vitro experiments further demonstrated that MAGL11 exerted its pro-healing effects by promoting the activation of the Rap1/PI3K/Akt signaling pathway. Specifically, MAGL11 enhanced the migration and chemotaxis of fibroblasts (NIH3T3), human umbilical vein endothelial cells (HUVECs), and keratinocytes (HaCaT) while simultaneously inhibiting cellular apoptosis-all of which collectively contributed to improved wound healing. Conclusions: These findings suggest that MAGL11 holds promise as a potential candidate for diabetic wound therapy, primarily through its ability to promote angiogenesis, fibroblast activation, and epithelial regeneration.

Background/Objectives: The global rise in multidrug-resistant (MDR) bacteria, particularly methicillin-resistant and methicillin-susceptible Staphylococcus aureus (MRSA and MSSA), continues to pose a major public health challenge, including in Hawaii. This underscores the need to discover new antimicrobial agents from natural sources. Guided by teachings from a Buddhist master regarding the medicinal value of lichens, we investigated the endemic Hawaiian lichen Cladonia skottsbergii. Methods: Specimens of C. skottsbergii were collected from the Lotus Buddhist Monastery in Mountain View, Hawaii. A methanolic extract was prepared and purified using chromatographic techniques, and compound structures were elucidated through spectroscopic analyses and single-crystal X-ray diffraction. The antibacterial activity of the compounds was assessed against Gram-positive strains (MRSA, MSSA) and Gram-negative bacteria (Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa). Cytotoxicity was assessed using A549 (non-small cell lung cancer) and Vero E6 (non-tumorigenic) cell lines. Results: Three compounds were isolated: clarosione (1), a newly identified trichlorinated xanthone, and two known metabolites, (S)-usnic acid (2) and perlatolic acid (3). Compounds 2 and 3 demonstrated strong inhibitory effects against MRSA and MSSA. Their minimum inhibitory concentrations (MICs) ranged from 2 to 4 µg/mL, compared with vancomycin (0.5-1 µg/mL). Cytotoxicity testing showed higher sensitivity in A549 cells than in Vero E6 cells, resulting in favorable selectivity indices for the active compounds. Conclusions: In the current study, a new compound, clarosione (1) was discovered. This enhances our understanding of the constituents of C. skottsbergii and its potential antibacterial properties. Lichen-derived compounds may serve as lead candidates for further development, and further study is warranted.

Bovine mastitis remains a major challenge in dairy production despite extensive antimicrobial use, with therapeutic failure increasingly attributed to factors beyond classical antimicrobial resistance (AMR). Growing evidence indicates that treatment inefficacy arises from the combined effects of pharmacokinetic/pharmacodynamic (PK/PD) constraints, biofilm-mediated tolerance, intracellular persistence, and the adaptive capacity of mastitis pathogens. Intramammary therapy is particularly limited by poor tissue penetration, episodic drug elimination via milk flow, and inactivation by milk components, frequently resulting in subtherapeutic exposure at the site of infection. These limitations are amplified in chronic and subclinical mastitis, where biofilms and intracellular reservoirs reduce antimicrobial susceptibility and promote relapse and resistance selection. This narrative review integrates current knowledge on pharmacokinetic and pharmacodynamic (PK/PD) barriers, microbial survival strategies, and antimicrobial resistance (AMR) mechanisms that underlie treatment failure in bovine mastitis. It critically evaluates conventional antimicrobial therapies alongside emerging approaches, including antimicrobial peptides, bacteriophages and endolysins, nanoparticle-based delivery systems, immunomodulators, CRISPR-guided antimicrobials, and drug repurposing strategies. Overall, available evidence highlights the potential of these approaches to enhance therapeutic durability, particularly in settings where biofilm formation, intracellular persistence, and resistance limit conventional treatment efficacy. By mapping research coverage across mastitis phenotypes and therapeutic outcomes, this review identifies key gaps in long-term efficacy and resistance mitigation and underscores the need for PK/PD-guided, biofilm-aware, and resistance-conscious strategies to support durable next-generation mastitis management.

Boron-dipyrromethene (BODIPY) dyes belong to a class of organoboron compounds that have become ubiquitous for researchers in areas of fluorescence imaging, photodynamic therapy, and optoelectronics. The intrinsic qualities of BODIPY dyes and their meso-modified structural analogs, Aza-BODIPY dyes, have propelled their recent increase in use in biomedical applications. The two scaffolds have high quantum yields, narrow absorption, and emission bandwidths with large Stokes' shifts, and high photostability and thermal stability. Because their properties are independent of solvent polarity and dye functionality, they can be tuned to promote novel analytical methods, resulting in the adaptation of the physicochemical and spectral properties of the dyes. In this review of BODIPY and Aza-BODIPY scaffolds, we will summarize their spectral properties, synthetic methods of preparation, and applications reported between 2014 and 2025. This review aims to summarize the advances in chemosensing, especially pH sensor development, and the advances in NIR-II window bioimaging probes. We hope that this succinct overview of Aza-BODIPY scaffolds will highlight their untapped potential, elucidating insights that may catalyze novel ideas in the physical organic realm of BODIPY.

Due to their therapeutic potential and effects on cells, exosomes derived from bovine colostrum (BCE) and milk (BME) are molecules that have been at the center of recent studies. Their properties include the ability to cross biological barriers, their natural biocompatibility, and their structure, which enable them to act as stable nanocarriers. Exosomes derived from milk and colostrum stand out in cancer prevention and treatment due to these properties. BMEs can be enriched with bioactive peptides, lipids, and nucleic acids. The targeted drug delivery capacity of BMEs can be made more efficient through these enrichment processes. For example, BME enriched with an iRGD peptide and developed using hypoxia-sensitive lipids selectively transported drugs and reduced the survival rate of triple-negative breast cancer (TNBC) cells. ARV-825-CME formulations increased antitumor activity in some cancer types. The anticancer effects of exosomes are supported by these examples. In addition to their anticancer activities, exosomes also exhibit effects that maintain immune balance. BME and BCE can regulate inflammatory responses with their miRNA and protein loads. These effects of BMEs have been demonstrated in studies on colon, breast, liver, and lung cancers. The findings support the safety and scalability of these effects. However, significant challenges remain in terms of their large-scale isolation, load heterogeneity, and regulatory standardization. Consequently, BMEs represent a new generation of biogenic nanoplatforms at the intersection of nutrition, immunology, and oncology, paving the way for innovative therapeutic approaches.

Background/Objectives: Malaria remains a major global health burden, increasingly complicated by resistance to artemisinin-based therapies. Because artemisinin activation depends on heme and porphyrin chemistry, we sought to exploit host red blood cell (RBC) heme metabolism as a therapeutic vulnerability. This study aims to develop and evaluate a host-directed "bait-and-kill" strategy that selectively sensitizes malaria-infected RBCs to artemisinin. Methods: We integrated quantitative proteomics, erythropoiesis transcriptomic analyses, flow cytometry, and in vitro malaria culture assays to characterize heme metabolism in mature RBCs and Plasmodium falciparum-infected RBCs (iRBCs). The heme precursor 5-aminolevulinic acid (ALA) was used to induce porphyrin accumulation, and dihydroartemisinin (DHA) was applied as the killing agent. Drug synergy, porphyrin accumulation, reactive oxygen species (ROS) induction, and parasite survival were assessed, including ring-stage survival assays using artemisinin-resistant clinical isolates. Results: Mature RBCs retain a truncated heme biosynthesis pathway capable of accumulating porphyrin intermediates, while uninfected RBCs are impermeable to ALA. In contrast, iRBCs exhibit increased membrane permeability, allowing selective ALA uptake and porphyrin accumulation. ALA alone did not induce cytotoxicity or ROS, whereas DHA induced ROS and parasite killing. The ALA + DHA combination resulted in synergistic parasite elimination, including complete clearance of artemisinin-resistant P. falciparum isolates from the Greater Mekong Subregion, with no recrudescence observed over three weeks of culture. Evidence supports a predominant role for host-derived heme metabolites in mediating this synergy. Conclusions: The bait-and-kill strategy selectively exploits host RBC heme metabolism to restore and enhance artemisinin efficacy while sparing uninfected cells. Using clinically safe compounds, this host-directed approach provides a promising, resistance-bypassing framework for malaria treatment and combination drug development.

Bacteriophage (phage) therapy, including monophage preparations, phage cocktails, engineered phages, and phage-derived enzymes, has re-emerged as a potential option for difficult-to-treat and biofilm-associated infections in the context of rising antimicrobial resistance. Recent scientific and regulatory developments, such as the 2024 World Health Organization Bacterial Priority Pathogens List and the introduction of the European Pharmacopoeia general chapter 5.31 on phage therapy medicinal products, highlight the growing interest in establishing quality, safety, and governance standards for clinical implementation. This narrative review provides an overview of current clinical applications of phage therapy, drawing on published case reports, case series, early-phase clinical studies, and regulatory experiences across different healthcare settings. Clinical use has been reported in respiratory, urinary tract, musculoskeletal, cardiovascular, and device-associated infections, particularly in cases involving multidrug-resistant pathogens, often in combination with antibiotics. At the same time, the biological characteristics of phages, such as strain specificity, adaptive composition of phage cocktails, and the need for individualized formulations, pose significant regulatory and translational challenges. Access to phage therapy currently relies on heterogeneous regulatory mechanisms, including compassionate use programmes, magistral preparations, named-patient pathways, and other national frameworks. Overall, phage therapy represents a promising strategy for selected infections, but its broader clinical adoption will depend on harmonized regulatory approaches, robust quality standards, and the generation of stronger clinical evidence to support safe and scalable use.

The blood-brain barrier (BBB) restricts therapeutic delivery to the central nervous system (CNS), hindering the treatment of neurological disorders, such as Alzheimer's disease, Parkinson's disease, brain cancers, and stroke. Aptamers, short single-stranded DNA or RNA oligonucleotides that can fold into unique 3D shapes and bind to specific target molecules, offer high affinity and specificity, low immunogenicity, and promising BBB penetration via receptor-mediated transcytosis targeting receptors such as the transferrin receptor (TfR) and low-density lipoprotein receptor-related protein 1 (LRP1). This review examines aptamer design through the Systematic Evolution of Ligands by Exponential Enrichment (SELEX) and its variants, mechanisms of BBB crossing, and applications in CNS disorders. Recent advances, including in silico optimization, in vivo SELEX, BBB chip-based MPS-SELEX, and nanoparticle-aptamer hybrids, have identified brain-penetrating aptamers and enhanced the brain delivery efficiency. This review highlights the potential of aptamers to transform CNS-targeted therapies.

Background/Objectives: One-dose packaging is beneficial for older adults and those on multiple medications because it ensures that no doses are missed and supports medication adherence. However, conventional one-dose packaging materials have high moisture permeability, making them unsuitable for the storage of hygroscopic medications. We evaluated the barrier performance of food packaging materials against moisture and oxygen and investigated their potential to enhance the physical stability of the highly hygroscopic sodium valproate, under stressed storage conditions. Methods: Barrier performance was evaluated by measuring the water vapor transmission (WVTR) and oxygen transmission rates of each packaging material. Then, we evaluated the stability of sodium valproate tablets in different food packaging films by measuring weight change, breaking force, and visual appearance over 14 days under stressed storage conditions (35 °C and 75% relative humidity). Conventional cellophane-laminated polyethylene was used as the reference. Results: The WVTR of the food packaging films were below 2 g/m²/day, less than that of the conventional material. Tablets stored in Materials A and B showed weight increases of no more than 1.2% after 3 days, whereas the maximum increase among all food films was 3.7% (Material C). For Materials A and B, the breaking force remained measurable and the visual appearance unchanged throughout the 14-day period, whereas Material C became unmeasurable by day 14. Tablets packaged in cellophane-laminated polyethylene exhibited deliquescence, with visible deformation and stickiness within 3 days, rendering them unmeasurable. Conclusions: Food packaging materials with high barrier performance offer a practical, safe, and effective solution for one-dose packaging of hygroscopic medications, potentially expanding their clinical use and improving adherence.

Optimizing immunosuppressant dosing presents significant challenges in kidney transplantation due to narrow therapeutic ranges and considerable inter-patient pharmacokinetic differences. Emerging strategies for precision dosing, encompassing Bayesian population pharmacokinetic models, pharmacogenomic integration, and artificial intelligence algorithms, aim to enhance drug monitoring by moving beyond traditional trough-based approaches. This review critically assesses available evidence for predictive dosing models targeting immunosuppressants, including calcineurin inhibitors, antimetabolites, and mTOR inhibitors in kidney transplant patients. Available observational and simulation studies demonstrate substantial methodological diversity, with Bayesian PopPK-guided strategies showing 15-35% better target exposure achievement compared to trough-based monitoring. The absence of pooled estimates precludes a precise summary effect size, and evidence from randomized controlled trials remains limited. Machine learning models, particularly for tacrolimus, frequently reduced prediction error relative to traditional regression approaches, but substantial heterogeneity in study design, outcome definitions, and external validation limits quantitative synthesis. Hybrid Bayesian-AI frameworks and explainable AI tools show conceptual promise but are largely supported by proof-of-concept studies rather than reproducible clinical implementations. Overall, Bayesian pharmacokinetic modelling represents the most mature and clinically interpretable approach for precision dosing in transplantation, whereas AI-driven and hybrid systems remain investigational. Key gaps include the need for standardized reporting, rigorous risk-of-bias assessment, prospective validation, and clearer regulatory and implementation pathways to support safe and equitable clinical adoption.