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Creative Nursing Volume 32 Issue 2 introduced critical qualitative research as part of the series on Critical Approaches for Nursing Research. This third article continues the series by offering an overview of critical mixed methods research (cMMR). As nurse researchers increasingly recognize the limitations of single-method inquiry for addressing complex equity issues, cMMR offers a powerful approach that integrates qualitative and quantitative methodologies through a critical lens. Drawing on two recently proposed frameworks (Hernandez-Johnson and Bendixen's 11-phase process and Younas, Kvist, and Stolt's conceptual framework), this article outlines the philosophical foundations, core features, and practical considerations for designing and conducting cMMR in nursing. The next editorial in the series will address queer research methods.
Carbapenem-resistant Enterobacterales (CRE) infections pose a global health concern owing to their increasing incidence and limited treatment options. Ceftazidime-avibactam (CAZ-AVI) has emerged as a promising therapeutic option, with some studies reporting improved outcomes in CRE bacteremia. However, evidence regarding its survival benefit remains unclear, particularly in Korea. In this retrospective cohort study, we compared the effectiveness of CAZ-AVI with the best available therapy (BAT) in patients with CRE bacteremia. We included adult patients with CRE bacteremia treated at a tertiary hospital between January 2022 and July 2024. Patients were grouped based on receipt of CAZ-AVI within 5 days of blood culture versus the BAT. The 14-day mortality was compared between the two groups using Pearson's χ² test and the log-rank test. Multivariable Cox regression was performed to evaluate the independent association between CAZ-AVI use and 14-day mortality. Among 194 patients, 32 (16.5%) and 162 (83.5%) received CAZ-AVI and BAT for CRE bacteremia, respectively. The 14-day mortality rate was significantly lower in the CAZ-AVI group than in the BAT group (12.5% vs. 32.1%, P = 0.043). Kaplan-Meier analysis showed improved 14-day survival with CAZ-AVI (log-rank test, P = 0.027). Multivariable analysis showed that CAZ-AVI use (hazard ratio [HR], 0.34; 95% confidence interval [CI], 0.12-0.98; P = 0.046) was significantly associated with reduced mortality, whereas chronic kidney disease (HR, 2.23; 95% CI, 1.09-4.59; P = 0.029), Pitt bacteremia score (HR, 1.10; 95% CI, 1.01-1.20; P = 0.027), and neutropenia (HR, 2.28; 95% CI, 1.00-5.19; P = 0.049) were associated with increased mortality. CAZ-AVI use was associated with improved survival in CRE bacteremia and can be considered for therapy.
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We investigated whether propofol (PPF) combined with salvianolic acid A (SAA) confers synergistic cardioprotection in diabetic sepsis. Diabetic-septic mice and high-glucose/LPS-treated cardiomyocytes were treated with PPF and SAA. Cardiac function, reactive oxygen species (ROS), inflammation, and the SIRT1/HMGB1 pathway were assessed. PPF combined with SAA synergistically attenuated cardiac inflammation, pyroptosis, and dysfunction, accompanied by SIRT1 upregulation and HMGB1 downregulation. Notably, low-dose coadministration of PPF (12.5 µM) and SAA (12.5 µM) achieved protection comparable to high-dose PPF (25 µM), significantly reducing ROS and pyroptosis markers. These protective effects were reversed by SIRT1 inhibition or silencing but enhanced by HMGB1 inhibition. PPF and SAA synergistically inhibit LPS-induced myocardial pyroptosis under hyperglycemia by activating the SIRT1/HMGB1 pathway. This combination offers a potential strategy to enhance cardioprotection while minimizing anesthetic dosage.
Histone deacetylase 6 (HDAC6) is a unique class IIb enzyme characterized by dual catalytic domains and predominant cytoplasmic localization, which underlies its involvement in cytoskeletal dynamics, neurodegenerative, and oncogenic pathways. These distinctive features have positioned HDAC6 as an attractive and challenging target for the development of selective inhibitors. In this review, we critically evaluate reported 2D/3D-QSAR studies of selective HDAC6 inhibitors, including CoMFA, CoMSIA, GRIND, and machine learning-based approaches. Relevant studies were identified through systematic searches of PubMed and Google Scholar between 2003 and 2025. A comparative analysis of the QSAR literature reveals a consistent structureactivity relationship, including the importance of cap group bulkiness for HDAC6 selectivity, the contribution of linker architecture to potency, and the dominant use of hydroxamic acid as a zinc-binding group, although non-hydroxamic acid gained significant attention. However, the predictive reliability of current QSAR models remains limited by small and chemically homogeneous datasets, insufficient external validation, and narrow biological endpoints. These limitations partially explain why only a small number of selective HDAC6 inhibitors have progressed into clinical evaluation, where suboptimal pharmacokinetic and druggability profiles remain major barriers. Overall, this review highlights the need for next-generation QSAR strategies that integrate larger, diverse datasets and structure-informed modeling to support the rational design of clinically viable selective HDAC6 inhibitors.
The pathogenesis of allergic rhinitis (AR) involves hyperreactivity of both the immune and neural systems. While sensory nerves detect allergens and release neuropeptides that directly participate in immune regulation, their precise role within the AR inflammatory network remains incompletely elucidated. Using house dust mite (HDM) and ovalbumin (OVA)-induced murine AR models, we selectively silenced nasal TRPV1-expressing sensory nerves pharmacologically with QX-314 (co-administered with capsaicin) and Resiniferatoxin (RTX). The effects of neuronal silencing on animal behavior, allergen-specific IgE levels, inflammatory cell nfiltration, and immune cell populations were systematically evaluated via immunofluorescence, histological staining, ELISA, and flow cytometry. Both QX-314 and RTX effectively silenced TRPV1+ sensory neurons in the trigeminal ganglia and significantly downregulated the expression of neuropeptides CGRP and SP. Silencing nasal TRPV1+ sensory nerves markedly reduced eosinophilic infiltration and levels of the associated marker ECP in the nasal mucosa of AR model mice. Unexpectedly, it also led to a significant increase in neutrophilic infiltration and MPO-positive cells. RTX-mediated ablation further compromised epithelial barrier integrity and aggravated the local inflammatory burden. Flow cytometric analysis further confirmed that RTX-mediated ablation of TRPV1+ neurons significantly decreased the proportions of infiltrating eosinophils and B cells, but increased the proportion of neutrophils in the OVA model. Silencing nasal TRPV1+ sensory nerves exerts a dual immunomodulatory effect in AR, attenuating eosinophilic inflammation while promoting neutrophilic infiltration. This reveals a critical neuro-immune balance in the nasal mucosa and suggests that precisely targeted neuromodulation strategies are required to suppress allergic inflammation.
Previous research has shown that the International Hip Outcome Tool (iHOT-33) and its short version (iHOT-12) have shown sufficient psychometric properties, but evidence as to which instrument has the best measurement properties is lacking. To perform a simultaneous comparison of the psychometric properties of the iHOT-33 and iHOT-12 in patients with symptomatic hip and groin disorders. After translation and cross-culturally adaptation into the Italian language, iHOT-33 and iHOT-12, along with other different instruments, were administered to 117 adults with musculoskeletal hip pain. Feasibility (floor/ceiling effect), structural validity (confirmatory factor analysis [CFA]), internal consistency (Cronbach's alpha [α]), test-retest reliability (intraclass correlation coefficient [ICC3,1]), measurement error (Minimal Detectable Change [MDC95]) and construct validity (hypothesis testing) were assessed. Feasibility was supported (no floor/ceiling effect). CFAs showed a one-factor structure for iHOT-33 (comparative fit index [CFI]=0.989; Tucker-Lewis index [TLI]=0.983; root means square residual [RMSEA]=0.034; standardized root mean square residual [SRMR]=0.054) and iHOT-12 (CFI = 0.989; TLI = 0.985; RMSEA = 0.042; SRMR = 0.045). Internal consistency was acceptable for iHOT-33 (α = 0.975) and iHOT-12 (α = 0.922). Test-retest reliability was good for iHOT-33 (ICC = 0.806) and iHOT-12 (ICC = 0.830). Measurement errorswere quite high (MDC95 = 24.8and 22.8 points for iHOT-33 and iHOT-12, respectively). Construct validity was satisfactory for each instrument (100%a-priori hypotheses met). iHOT-33 and iHOT-12 were found to be reliable and valid. However, the measurement error could be high for both instruments; however iHOT-12 presented a lower measurement error. Therefore, iHOT-12 should be preferred if compared to iHOT-33 fordisability assessment in patients with symptomatic hip and groin disorders.
Despite the large use of renin-angiotensin system inhibitors (RASI) in STSegment Elevation Myocardial Infarction (STEMI) patients, few data have been reported on the prognostic impact of chronic RASI at admission in patients suffering from STEMI, especially during the COVID-19 pandemic. Therefore, the current study investigated the prognostic impact of chronic RASI at admission in patients suffering from STEMI, including both SARS-CoV-2 positive and negative individuals, enrolled before and during the COVID-19 pandemic. We included STEMI patients who received primary percutaneous coronary intervention (PPCI) and were enrolled in the ISACS-STEMI COVID-19 registry. In the present sub-analysis, patients were allocated according to chronic RASI therapy at admission. The primary study endpoint was the occurrence of in-hospital mortality. Secondary endpoints were postprocedural TIMI 3 flow and mortality at 1 month. The overall population was 15,693 patients, including 6,213 patients pretreated with RASI. Several differences in baseline characteristics were observed between the two groups. No difference was observed in the prevalence of SARS-CoV-2 infection. After correction for all baseline confounders, including procedural features, chronic pretreatment with RASI was independently associated with improved postprocedural TIMI 3 flow (OR [95% CI] = 1.14 [1.03-1.35], p = 0.042), lower in-hospital mortality (adjusted OR [95% CI] = 0.64 [0.54-0.75], p < 0.001), and lower 30-day mortality (adjusted OR [95% CI] = 0.62 [0.53-0.73], p < 0.001). This is the largest study investigating the prognostic impact and benefits of chronic RASI pre-treatment in STEMI patients undergoing PPCI, including those treated during the COVID19 pandemic. We found that chronic RASI treatment at hospital admission was associated with significant improvement in reperfusion and reduction in mortality, without any negative effect in SARS-CoV-2 positive patients. Results should be interpreted considering the retrospective, nonrandomized nature of the study.
Ferroptosis, a form of regulated cell death characterized by iron-dependent lipid peroxidation, plays a critical role in various diseases. Berberine, a bioactive compound from plants such as Coptis chinensis, tree turmeric, and barberry, exhibits bidirectional regulation of ferroptosis, but its systemic mechanisms remain unclear. This review summarizes berberine's effects through multiple signaling pathways, emphasizing context-dependent mechanisms, tissue-specific accumulation, and therapeutic potential. Relevant literature was retrieved from PubMed, Web of Science, CNKI, and ScienceDirect. Berberine modulates ferroptosis via iron homeostasis, lipid peroxidation, the System Xc-/GSH/GPX4 anti-oxidant system, and mitochondrial function, involving NRF2, p53, AMPK, PI3K/Akt, and MAPK pathways. It promotes ferroptosis in tumors and fibrotic diseases but inhibits it in cardiovascular, metabolic, and neurological disorders, alleviating tissue damage. Nano-delivery systems and structural optimization enhance bioavailability and targeting, demonstrating therapeutic efficacy and biosafety. Berberine's multi-target, bidirectional regulation shows promising clinical potential, warranting further mechanistic and delivery-focused studies.
Preferences for advanced hearing aid (HA) noise management features, such as directionality and noise reduction (DIR + NR), differ significantly among users. Due to the lack of standardized clinical guidelines for fine-tuning these features, audiologists often rely on individual user preferences. However, this approach doesn't always ensure optimal hearing outcomes. The goal of this study was to examine how users respond to these advanced features in everyday acoustic environments, with two main goals: to assess how sensitive users are to changes in DIR + NR settings compared to subtle gain adjustments, and to identify the factors influencing DIR + NR preferences in various situations. A total of 123 individuals using bilateral HAs participated in the study, conducted at two locations in Germany and Japan. Over six testing periods (half a year), participants were provided with two listening programs that differed either in the strength of their DIR + NR settings or in gain levels for high-frequency and soft sounds. Participants documented their preferences via self-initiated questionnaires, reporting experiences with the different settings in real-life listening scenarios. Most participants preferred modest adaptive DIR + NR settings and participants generally expressed higher preference strength for small gain changes than for variations in DIR + NR. Preferences could not be reliably predicted from audiologic or environmental factors, apart from a minor influence of subjective noisiness. These findings suggest that clinicians can guide the initial fitting of DIR + NR settings to optimize speech-in-noise performance, as adaptive DIR + NR configurations are broadly acceptable. User preferences remain important, particularly during gain fine-tuning, as small adjustments can be noticeable.
Patients with infantile- and late-onset Pompe disease (IOPD/LOPD; PD) experience progressive motor deficits. Current methods for assessing muscle health, such as motor tasks or magnetic resonance imaging (MRI), are limited in young or severely affected individuals. This study evaluated electrical impedance myography (EIM) as a noninvasive biomarker of muscle health in PD. Sixty-four participants (11 IOPD, 27 LOPD, 26 healthy controls) were assessed. EIM phase and reactance values were obtained from bilateral limb muscles. Twenty PD participants underwent lower limb musculoskeletal MRI. Participants completed Perceived Stress Scale-10 and Patient-Reported Outcomes Measurement Information System questionnaires. Motor performance was evaluated via balance tests, 9-Hole Peg Test, grip strength, 2-Minute Walk Test, and 4-Meter Walk Test. Participants with PD reported greater impairment in pain intensity, mobility, physical stress experience, and physical function, and performed worse on motor tasks than healthy controls (all p<0.05). EIM phase at 100 and 211 kHz was reduced in participants with PD, particularly in those with IOPD and in pediatric PD participants, compared to healthy controls. Lower phase correlated with higher MRI fat fraction and poorer motor performance. With additional longitudinal investigation, EIM may represent a functionally relevant, noninvasive tool to evaluate disease severity in individuals with PD.
Antimicrobial resistance (AMR) is a major global concern, with pathogens such as E. coli, B. subtilis, P. aeruginosa, and S. aureus showing increasing resistance to conventional antibiotics. Piperazine, a six-membered heterocyclic scaffold, is widely used in drug design due to its flexibility and diverse biological activities. A new series of piperazine derivatives was synthesized with aromatic and heterocyclic substituents. The compounds were characterized using spectroscopic and physicochemical techniques. Their antibacterial activity was evaluated in vitro against Gram-positive and Gram-negative bacteria using the cup-plate method, with ciprofloxacin employed as the standard reference drug. Molecular docking studies and in silico ADME/Tox analyses were performed to assess protein binding, pharmacokinetic properties, and toxicity. Based on the results, a structure-activity relationship (SAR) analysis was also carried out. Among the synthesized derivatives, compound 13 exhibited the most potent broad-spectrum antibacterial activity, showing maximum inhibition against Bacillus subtilis (21.3 mm) along with notable activity against Escherichia coli and Staphylococcus aureus. Molecular docking studies revealed strong binding affinity toward DHFR from S. aureus (-10.60 kcal/mol) and ankyrin repeat protein from B. subtilis (-9.02 kcal/mol). Additionally, in silico ADME/Tox predictions suggested favorable oral bioavailability, low toxicity risk, and minimal inhibition of CYP enzymes. The SAR analysis showed that piperazine derivatives containing well-placed electron-withdrawing groups and balanced physicochemical properties displayed improved antibacterial activity, with compound 13 emerging as the most potent due to its strong molecular interactions. SAR analysis indicated that electron-withdrawing substituents on the piperazine core enhanced antibacterial potency. The combination of structural modification, strong protein binding, and favorable pharmacokinetic properties explains the superior activity of compound 13. Compound 13 emerges as a promising broad-spectrum antibacterial agent. The study demonstrates the potential of SAR-guided piperazine derivatives for developing novel antibacterial therapeutics and supports further in vivo evaluation and structural optimization.
Use of oral nicotine pouches, and specifically the brand Zyn, has increased among all age groups in the United States (U.S.), and these products have a wide advertising and social media presence. The purpose of our study was to identify prevalence and correlates of oral nicotine pouch use, Zyn use, and Zyn susceptibility in the U.S. and identify sources of advertising exposure for Zyn. We conducted a cross-sectional survey. We conducted an online national survey in the U. S, through Qualtrics, from March-June 2025. Participants were 13-40-year-olds (N = 5733), with a 1:1:1 ratio of people ages 13-17, 18-20, and 21-40; 66.1% were female. We asked participants about lifetime and past 30-day oral nicotine pouch use, Zyn use in particular, susceptibility to use Zyn, use of Zyn flavors, detailed patterns of Zyn use, and exposure to Zyn advertising, overall and stratified by age group. Among our sample, lifetime use of any nicotine pouch and Zyn specifically were 11.5% and 9.3%, respectively; past 30-day use of any nicotine pouch and Zyn specifically were 5.0% and 3.9%, respectively. Lifetime use and past 30-day use increased across age groups. Among those who had never used any nicotine pouch, 27.6% were susceptible to Zyn use. Using logistic regressions, we identified correlates to oral nicotine pouch use and Zyn susceptibility, including covariates for age group, sex, race/ethnicity, financial comfort, e-cigarette use, and cigarette use. Increasing age group and e-cigarette and cigarette use were associated with any oral nicotine pouch use and Zyn susceptibility. The most popular Zyn flavors ever used were mint (n = 388) and drinks (n = 190). On average, participants with past 30-day Zyn use reported a median of using 4.0 (interquartile range [IQR]: 4.0) pouches per day; a median of placing 2.0 (IQR: 3.0) pouches in their mouth at once; and a median of using 2.0 (IQR: 2.0) cans of Zyn per week. TikTok (18.2%, n = 1044), YouTube (17.8%, n = 1021), and Instagram (16.3%, n = 935) were the top platforms participants reported ever seeing a Zyn advertisement or promotion. A United States national survey found substantial rates of use, susceptibility to use, and exposure to marketing for Zyn and other oral nicotine pouches. Mint and drinks were the most commonly used Zyn flavors.
CuTaS3, an important member of the bimetallic chalcogenide family, stands out because of its nontrivial physicochemical properties and potential applications in electronic and optoelectronic devices. Despite the extensive investigations into structural characterizations and device applications, the knowledge about structural and electronic transitions of CuTaS3 under high pressure is deficient. In this work, we filled these research gaps and explored the high-pressure structural, vibrational, and electrical transport properties of CuTaS3 under different hydrostatic environments by virtue of Raman spectroscopy, microarea X-ray diffraction (XRD), and electrical conductivity measurements. Upon nonhydrostatic compression, CuTaS3 experienced two successive phase transitions at 2.2 and 5.4 GPa and sequential metallization at 12.5 GPa. Nevertheless, the pressure-induced structural and electronic transitions of CuTaS3 were unsusceptible to hydrostaticity, which was attributed to the faint deviatoric stress at ∼10.0 GPa under different hydrostatic environments. Upon depressurization, the phase transition was revealed to be incompletely reversible under different hydrostatic environments with the preservation of pressure effects or the existence of a kinetic barrier. Additionally, CuTaS3 exhibited Ohmic behavior at high pressures. These findings on CuTaS3 pave the way for exploring the physicochemical properties of other bimetallic chalcogenides under extreme conditions, thereby facilitating its potential applications in other promising fields.
The study addresses the urgent need to evaluate groundwater security in a fast-growing megacity challenged by complex geogenic and anthropogenic threats. Thus, the main objective was to study the occurrence, geochemical behavior and radiation risk of radium isotopes (226Ra and 228Ra) and heavy metal contamination in groundwater samples of Dhaka City, Bangladesh. Hydrochemical analysis showed that reverse ion-exchange and silicate weathering control the groundwater chemistry rather than evaporation trends. Heavy metals were at low-to-medium levels of pollution according to the contamination index (Cd); however, the Heavy Metal Evaluation Index (HEI) identifies isolated areas of significant contamination. Notably, mercury (average 1.97 ± 0.16 µg L-1) exceeds safety thresholds. The 3H activities suggested that the groundwater was young and hosted in unconsolidated sand-rock aquifers radiologically. Combined radium activities were above the USEPA threshold (0.185 Bq L-1) and 226Ra, 228Ra and 40K were above WHO guidelines, with higher 228Ra activity. The spatial distribution analysis showed relatively higher radium enrichment in the northern and north-eastern parts of the studied area. Radium mobilization was governed by the reduced adsorption capacity controlled by ambient redox conditions, elemental concentrations, and the natural processes such as α-recoil, mineral dissolution and desorption from aquifer materials. The annual effective doses were higher than the WHO limits and excess lifetime cancer risk (ELCR) indicates 228Ra as the main radiological risk. Broader implications highlight significant, interrelated geochemical and radiological health risks to Dhaka's water supply. These results give crucial details for the sustainable management of groundwater operations, especially in areas where groundwater resources are limited.
Polycyclic aromatic hydrocarbons with multiple-resonance (MR) effect are emerging as leading candidates for wide-color-gamut displays. However, it remains a significant challenge to red-shift their emissions to long wavelengths without sacrificing the spectral full width at half maximum (FWHM). Herein, a synergistic strategy of aromaticity localization and tetraboron extension is newly proposed, in which a B‒N covalent-bond-fused MR core is fused with 5,10-dihydro-5,10-diphenylphenazine (DPPA) to afford two yellow-emitting narrowband tetraboron emitters. By integrating multiple local B-π-B motifs into a rigid square-like tetraboron MR framework, DPA-4B and DMAC-4B achieve a pronounced red shift from violet-blue DPA-1B to yellow emission. The antiaromatic N2C4 ring and surrounding nonaromatic 1,2-BN/1,4-BN heterocycles promote aromaticity localization and suppress excited-state relaxation, affording narrow emissions at 544-559 nm with FWHMs of 20-21 nm. The DPA-4B and DMAC-4B-based sensitized OLEDs further achieve narrowband yellow electroluminescence with maximum EQE values of 36.7% and 30.1%, respectively. These results demonstrate that the combination of aromaticity localization and tetraboron extension is a promising molecular design rule for simultaneously realizing emission red-shifting, spectral narrowing, and device efficiency in B‒N covalent-bond-containing MR emitters.
The TGF-β signaling pathway plays a dual role in cancer, acting as both a tumor suppressor and a potent driver of metastasis and immune evasion. Traditional TGF-β inhibitors, primarily ATP-competitive kinase blockers, have faced clinical hurdles including systemic toxicities and compensatory resistance. This review provides a medicinal chemistry-oriented perspective on the fundamental transition from occupancy-based inhibition to event-driven targeted protein degradation (TPD). We systematically analyze the chemical evolution of TGF-β modulators, highlighting how rational SAR optimization-such as linker rigidification and the selection of tissue-specific E3 ligases-enhances ternary complex stability and catalytic efficiency (DC50). Furthermore, we discuss the transformative role of artificial intelligence (AI) and molecular docking in guiding the design of next-generation bifunctional degraders, including PROTACs and LYTACs. By synthesizing cuttingedge research and clinical data, this article outlines a roadmap for dismantling the TGF-β axis, offering strategic insights for the development of more potent, selective, and safer therapeutic agents.
Ionising radiation induces various types of DNA damage, which, if not repaired correctly, lead to mutations. Nonetheless, the association between radiation exposure and hereditary effects has not yet been confirmed in humans. In this study, we used WGS to study low dose rate radiation-induced mutations in cultured human cells. Normal human fibroblast NB1RGB cells were seeded as single cells by limiting dilution and grown under irradiation with 137Cs γ-irradiation of 1 or 20 mGy day-1 for 21 days. The genomic DNA prepared from respective clones or the bulk culture was sequenced using the Illumina NGS platform with paired-end 150-bp reads with reference to the standard human genome assembly GRCh38. By subtracting the calls in the bulk culture and applying several filters, approximately 750-1200 single-nucleotide polymorphisms (SNPs) and 2500 small insertions/deletions (indels) per clone were obtained on average. The number was not substantially different between unirradiated and irradiated cultures. Spectral analysis revealed that the C > A transversion, which is associated with guanine oxidation, was dominant.
Keratitis is a critical inflammation of the cornea caused by chemical agents due to bacterial, fungal, or viral pathogens. It significantly contributes to the global burden of vision loss and blindness in older adults. Antimicrobial treatment helps fight different types of bacteria. Conventional treatments are less effective owing to poor ocular drug bioavailability, rapid tear clearance, and drug-resistant microbes. Recent developments in nanotechnology hold promise for circumventing these limitations via improved delivery, targeting, and combination therapies. This study provides a critical review of the pathogenesis of microbial keratitis and a systematic assessment of emerging therapeutic approaches based on nanotechnology, including piezodynamic therapy (PZDT), photothermal therapy (PTT), photodynamic therapy (PDT), nanoenzymes, and metal ions. The assessment of each modality is based on its mechanism of action, effectiveness against biofilm-embedded pathogens, ability to modulate immune responses, and potential use with advanced drug delivery systems, such as microneedle patches, functionalized nanoparticles, and responsive hydrogels. This review also highlights the role of nanocarriers in improving drug retention, reducing systemic toxicity, and enabling targeted drug delivery to infected corneal tissue. Toxicity, regulatory hurdles, and therapeutic consistency pose challenges to clinical translation. This review presents a comprehensive outlook on the potential of nanomedicine in keratitis therapy using microbiology, immunology, materials science, and clinical ophthalmology. The goal is to inform future research and foster interdisciplinary approaches that will result in treatments that are more effective, safer, and patient-focused for this vision-impairing condition. Nanotechnology-enabled ocular therapies may overcome existing drug delivery limitations and improve clinical outcomes in microbial keratitis, as noted in this review.
Psychological stress promotes cancer metastasis through activation of catecholamine-mediated β-adrenergic signaling. Bupleurum falcatum L. (BF) root has traditionally been used to treat stress-related disorders attributed to qi stagnation. This study investigated the anti-metastatic effects of an ethanolic extract of BF root (EBF) in chronic stress-induced cancer metastasis. EBF significantly suppressed adrenergic agonist-induced migration and invasion in MDA-MB-231 breast cancer and Hep3B hepatocellular carcinoma cells. In a chronic stress-induced lung metastasis mouse model, EBF markedly reduced lung metastasis of 4T1 breast cancer cells. Network pharmacology analysis and experimental validation identified Src as a key mediator of the anti-metastatic effects of EBF. Liquid chromatography-mass spectrometry (LC-MS) analysis confirmed the presence of major saikosaponins, and among them, saikosaponin D (SSD) showed notable inhibitory effects on cancer cell migration and Src phosphorylation. Molecular docking analysis further suggested a potential direct interaction between SSD and Src. These findings demonstrate that EBF attenuates chronic stress-induced cancer metastasis by inhibiting Src activation, supporting the traditional concept of soothing the liver and regulating qi as a therapeutic strategy for managing stress-related tumor progression.