Bacterial infections of the anterior segment of the eye remain difficult to manage due to rapid precorneal clearance, limited corneal permeability, and short residence time associated with conventional ophthalmic formulations. These challenges often necessitate frequent dosing, which may reduce patient adherence and therapeutic efficiency. Ofloxacin, a broad-spectrum fluoroquinolone antibiotic, is commonly used for ocular infections; however, its topical effectiveness is limited by poor corneal penetration and low ocular bioavailability. Therefore, this study aimed to develop and characterize ofloxacin-loaded hybrid polymeric nanomicelles based on D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) and Poloxamer 188 (P188) and to evaluate their in vitro release profile and ex vivo transcorneal permeation as a strategy to improve the topical ocular delivery potential of ofloxacin. Ofloxacin-loaded nanomicelles were prepared using TPGS and P188 via the thin-film hydration technique. The effect of polymer composition on micellar characteristics, drug encapsulation, release behavior, and corneal permeation was systematically evaluated. The optimized formulation (F8), composed of 30 mg TPGS and 20 mg P188, exhibited a small particle size (14.61 ± 0.06 nm), narrow size distribution (polydispersity index [PDI], 0.158 ± 0.02), mildly negative zeta potential (−6.47 ± 0.4 mV), and high entrapment efficiency (88.7 ± 0.92%). In vitro release studies showed a sustained release profile, with approximately 80% drug release over 10 h, compared with less than 25% from the pure ofloxacin suspension. Ex vivo transcorneal permeation studies using excised sheep cornea demonstrated significantly enhanced drug transport, characterized by increased steady-state flux and reduced lag time. Overall, the findings indicate that hybrid polymeric nanomicelles represent a promising platform for improving the biopharmaceutical performance and corneal transport of topical ofloxacin eye drops. In vivo ocular residence time and clinical antibacterial efficacy were not assessed in this study and should be explored in future investigations. Graphical abstract :
Root cultures (RC) of Linum alpinum and L. austriacum (Linaceae) were investigated for enhanced arylnaphthalene-type lignan production through precursor feeding with coniferyl alcohol (CA). Monitoring the accumulation of justicidin B (JB), as a target metabolite, over a 30-day cultivation period revealed different accumulation profiles in the two species. Both RC were treated with 10, 50, or 100 µM CA on day 25 of cultivation and harvested 5 days later. CA supplementation exerted only a limited effect on JB accumulation in L. alpinum , with the highest level recorded at 100 µM. In contrast, L. austriacum responded more markedly, with 50 µM CA yielding the maximum JB content (1.49 µg/mg DW), representing an approximately twofold increase compared with untreated controls. Further treatment at later cultivation stages confirmed a cultivation-stage-dependent response in L. austriacum and supported 50 µM CA as the most effective precursor-feeding condition. The phytochemical potential, production capacity, and precursor biotransformation capacity of in vitro plant systems are largely governed by the genetic background of the donor species. In addition, in vitro cultures of two related species frequently display marked differences in their metabolic and biosynthetic profiles.
In vitro root cultures (RCs) of Linum alpinum and L. austriacum (Linaceae) were used as model systems to investigate phenylpropanoid pathway regulation and justicidin B (JB) accumulation in response to exogenous vitexin supplementation. JB was quantified by LC-HRESI-MS over a 30-day cultivation period following vitexin treatment at different concentrations and developmental stages. Vitexin exerted species-, concentration-, and stage-dependent effects on JB accumulation. In L. alpinum , vitexin induced a modest increase at 1 μM (1.2-fold), whereas L. austriacum showed a stronger concentration- and cultivation-stage-dependent response. The highest fold increase was observed following treatment with 10 μM vitexin on day 35. The results of this study suggest that exogenous flavonoid supplementation may influence metabolic distribution within the phenylpropanoid network, potentially favoring arylnaphthalene lignan biosynthesis. The study highlights a possible regulatory interaction between flavonoid and lignan pathways in plant in vitro systems.
Identifying barriers to medication adherence can support the development of targeted interventions designed to improve adherence. This study aimed to identify medication adherence barriers in patients with diabetes, the demographic and health-related factors associated with these barriers, and the relationship between these barriers and the level of medication adherence. This cross-sectional study was conducted among patients with diabetes mellitus receiving outpatient care at three provincial public hospitals in Vietnam between January and March 2026. Exploratory factor analysis identified a three-factor empirical structure of medication adherence barriers, labeled medication management barriers, psychosocial barriers, and motivational barriers. Motivational barriers had the strongest correlation with medication adherence (r = –0.270, p < 0.001). These findings highlight motivational and psychosocial barriers as potential targets for future adherence-improving interventions in diabetes care.
Disruption of intestinal barrier integrity contributes to systemic inflammation. This study evaluated the immunomodulatory effects of Lentilactobacillus hilgardii DSB22 isolated from fermented bamboo shoots in a lipopolysaccharide (LPS)-challenged BALB/c murine model. Mice receiving oral administration of L. hilgardii DSB22 for 28 days showed significantly increased intestinal secretory immunoglobulin A (sIgA) levels following LPS challenge. Treatment also reduced tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) levels and increased interleukin-10 (IL-10) concentrations in serum and spleen homogenates. Histopathological analysis of the distal ileum demonstrated preservation of villus architecture and improved villus height-to-crypt depth ratios in probiotic-treated mice. No significant cytokine changes were observed in non-challenged animals receiving the strain. These findings suggest that L. hilgardii DSB22 exerts immunomodulatory effects and may help protect intestinal barrier integrity during inflammatory conditions.
An observational multicenter cohort study involving 120 patients treated with chemotherapy alone or in combination with pembrolizumab or atezolizumab was conducted. Interleukin-6 (IL-6) levels were measured after six cycles, and response of tumor was estimated with the Response Evaluation Criteria in Solid Tumors (RECIST). Receiver operating characteristic (ROC) analysis was conducted. IL-6 levels were significantly reduced in the chemo-immunotherapy groups compared with the chemotherapy group (p < 0.001). Patients with an objective response had lower IL-6 levels than non-responders (p < 0.001). Post-treatment IL-6 and the neutrophil-to-lymphocyte ratio (NLR) were tested, and both were significant in univariate analysis. However, only post-treatment IL-6 remained independently associated with progressive disease in multivariable analysis. ROC analysis revealed exceptional discriminative performance, with an area under the curve (AUC) of 0.961, 91.6% sensitivity, and 96.0% specificity. Therefore, post-treatment IL-6 was independently associated with disease progression and may demonstrate a promising biomarker for risk stratification in patients with non-small cell lung cancer (NSCLC) and chronic obstructive pulmonary disease (COPD).
Alcoholic liver disease (ALD) is characterized by hepatic steatosis, inflammation, and gut-liver axis dysfunction. Gabapentin, an antiepileptic agent commonly used in the management of alcohol withdrawal syndrome, has demonstrated potential anti-inflammatory properties. This study investigated the effects of gabapentin on alcohol-induced hepatic and intestinal injury using a zebrafish ( Danio rerio ) model. Adult zebrafish were exposed to 0.5% ethanol for 28 days, followed by gabapentin treatment for 2 or 4 weeks. Liver and intestinal tissues were collected for histopathological evaluation by hematoxylin and eosin staining. Bioinformatic analysis of a publicly available transcriptomic dataset was performed to identify differentially expressed genes associated with alcoholic hepatitis, while interleukin-8 ( il8 ) expression was evaluated using real-time quantitative PCR. Gabapentin treatment was associated with reduced hepatic steatosis and goblet cell hyperplasia during the post-ethanol recovery phase, accompanied by lower il8 expression. These findings provide insight into gut-liver axis dysfunction in ALD and support further investigation of gabapentin as a potential adjunctive therapy for alcohol-associated hepatic and intestinal injury.
Oridonin is a natural compound with anti-inflammatory and antioxidant activities; however, its use as a topical therapeutic option for psoriasis has received limited attention. The novelty of this research lies in the design and assessment of topical oridonin ointments and their comprehensive assessment in an imiquimod (IMQ)-induced mouse model of psoriasis-like inflammation through clinical, inflammatory, protein, and gene expression analyses. Thirty-six mice were divided into six groups and treated with paraffin ointment, oridonin ointment (1% or 2%), or mometasone furoate. Oridonin ointments were applied after psoriasis induction. Both formulations of oridonin significantly decreased inflammatory mediators, namely interleukin (IL)-23, IL-17, IL-6, tumor necrosis factor alpha (TNF-α), and nuclear factor kappa B (NF-κB), reduced malondialdehyde (MDA), decreased psoriasis severity, and improved skin thickness. The 2% formulation generally produced greater numerical improvements than the 1% formulation. These findings indicate that oridonin ointment is a promising therapeutic option for psoriasis management through its potent anti-inflammatory impact.
Pulmonary embolism (PE) is a serious and potentially fatal condition caused by obstruction of the pulmonary arterial system by thrombotic material. While the baseline risk in the general population remains low, it rises significantly in the presence of certain predisposing factors such as major surgery, malignancy, prolonged immobilization, and advanced age (Henke et al. 2020). Corticosteroid therapy increases the risk of venous thromboembolism (VTE) through both direct and indirect mechanisms. Directly, it induces a prothrombotic state by increasing procoagulant factors and suppressing fibrinolysis (Stuijver et al. 2013). Indirectly, long-term glucocorticoid (GCS) therapy causes secondary osteoporosis in 30–50% of patients, resulting in a 160% higher risk of vertebral fractures (Kobza et al. 2021). Major osteoporotic fractures are themselves independent risk factors for VTE (Ventrapragada et al. 2024). Furthermore, these fractures can lead to immobilization. Several underlying diseases and clinical conditions, such as chronic inflammatory diseases, significantly increase the risk of developing PE by promoting hypercoagulability, venous stasis, and endothelial injury, collectively known as Virchow’s triad (Shah et al. 2022). This case report describes a 41-year-old male patient who developed a massive pulmonary embolism shortly after neurosurgical intervention for multiple vertebral fractures. The fractures were associated with long-term corticosteroid therapy for ulcerative colitis. The patient required urgent embolectomy. This case highlights the importance of identifying risk factors associated with an increased incidence of pulmonary embolism, as this enables early detection of postoperative thromboembolic complications and prompt management, ultimately improving outcomes.
Background: Psoriasis is a chronic immune-mediated inflammatory skin disease characterized by excessive keratinocyte proliferation, persistent oxidative stress, and dysregulated inflammatory responses. Increasing evidence suggests that impaired antioxidant defenses and altered NLRP3-associated inflammatory signaling may contribute to psoriasis pathogenesis. Febuxostat, a selective xanthine oxidase inhibitor, has demonstrated antioxidant and anti-inflammatory effects in experimental models of various diseases; however, its potential as a topical treatment for psoriasis has not been investigated. Objective: The present study evaluated the therapeutic effects of topical febuxostat ointment in an imiquimod-induced mouse model of psoriasiform dermatitis and investigated its effects on oxidative stress biomarkers, inflammatory cytokines, and NFE2L2 (NRF2) and NLRP3 mRNA expression. Methods: Psoriasiform dermatitis was induced in BALB/c mice by daily topical application of 5% imiquimod cream. Animals were randomly assigned to the normal control, imiquimod control, clobetasol, and topical febuxostat treatment groups. Disease severity was evaluated using a modified PASI-like scoring system, clinical skin thickness assessment, and histopathological examination. Oxidative stress biomarkers, including malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), and nitric oxide (NO), were determined. Tissue concentrations of TNF-α, IL-17A, and IL-23 were quantified by ELISA, while NFE2L2 (NRF2) and NLRP3 mRNA expression levels were assessed using quantitative real-time PCR. Results: Topical febuxostat markedly attenuated imiquimod-induced psoriasiform dermatitis, as evidenced by reduced clinical severity and improvement in histopathological abnormalities, including epidermal hyperplasia and inflammatory cell infiltration. Febuxostat treatment significantly reduced MDA, NO, TNF-α, IL-17A, and IL-23 levels, while increasing SOD activity and GSH levels. Furthermore, febuxostat increased NFE2L2 mRNA expression and reduced NLRP3 mRNA expression, particularly at the 2% concentration. These molecular changes were associated with improved oxidative and inflammatory profiles but did not by themselves establish direct activation of the NRF2 pathway or inhibition of the NLRP3 inflammasome. Conclusion: Topical febuxostat demonstrated significant antipsoriatic effects in the imiquimod-induced mouse model, accompanied by improvements in oxidative stress, inflammatory cytokines, and histopathological abnormalities. The associated changes in NFE2L2 and NLRP3 mRNA expression suggest a potential contribution of altered redox- and inflammation-related gene expression to the observed therapeutic effects. However, protein-level and functional studies are required to determine whether these transcriptional changes translate into direct modulation of the NRF2/NLRP3 signaling pathways. These findings support further investigation of topical febuxostat as a potential nonsteroidal candidate for psoriasis.
Diabetic kidney disease (DKD) remains associated with substantial residual kidney and cardiovascular risk despite renin–angiotensin system blockade and sodium–glucose cotransporter 2 (SGLT2) inhibitor therapy. Routinely collected data from 16 adults with documented DKD who initiated finerenone 10 mg once daily at a single nephrology center were retrospectively analyzed. The primary outcome was the change in urine albumin-to-creatinine ratio (UACR); estimated glomerular filtration rate (eGFR), serum creatinine, serum potassium, and UACR responder rates were secondary outcomes. Measurements were assessed at baseline, 3 months, and 6 months. The mean age was 68.4 ± 9.6 years; 75.0% were women; the median baseline eGFR was 35.6 (interquartile range [IQR] 29.9–56.7) mL/min/1.73 m2; and the median baseline UACR was 57.0 (IQR 19.8–123.3) mg/g. Background angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker therapy and SGLT2 inhibitor therapy were each present in 93.8% of patients. Six-month data were available for 15 patients. Median UACR decreased to 30.0 mg/g at 3 months and 18.0 mg/g at 6 months (Friedman p < 0.001; Kendall’s W = 0.871). Median relative reductions were 28.4% and 54.1%, respectively. At 6 months, 12/15 patients (80.0%) achieved a ≥30% UACR reduction, and 9/15 (60.0%) achieved a ≥50% reduction. No statistically significant longitudinal change was detected in eGFR (p = 0.112) or serum potassium (p = 0.166). A post-baseline potassium value ≥5.5 mmol/L was observed in two patients; no value exceeded 5.5 mmol/L or reached 6.0 mmol/L. In this small uncontrolled cohort, finerenone initiation was associated with a marked reduction in UACR over 6 months. The findings are exploratory and should be interpreted cautiously because of the retrospective design, limited sample size, absence of a comparator, short follow-up, and potential confounding by concomitant therapies.
It was shown the comparative antimicrobial activity of postbiotics (bacteriocins and exopolysaccharides) isolated from lactic acid bacteria (LAB) strains of genus Enterococcus and Lactobacillus against three broad panelsof human pathogens. The antimicrobial activity was assessed in a concentration-dependent manner and compared with that of conventional antibiotics. Selected and purified bacteriocins from strains of L. rhamnosus 2012 and E. faecium KE5, for which an MIC of 5 mg/mL was established against S. typhimurium G-38 via the serial dilution method, exhibited the strongest antimicrobial activity across a broad panel of pathogens when tested at this concentration using agar diffusion assays. Postbiotics displayed strain-specific inhibitory effects, highlighting their narrower antimicrobial spectrum relative to antibiotics. It was shown that conventional antibiotics demonstrated broad-spectrum efficacy against susceptible strains but known failures against multidrug-resistant (MDR) isolates. Differences in antimicrobial effects between postbiotics may depend on their interaction with the cell membrane of pathogens. These findings suggest that LAB-derived postbiotics could serve as complementary antimicrobial agents (with antibiotics or another bioactive substance), which may have applications in nutritional and preventive frameworks.
Parenteral nutrition (PN) therapy is indicated to meet patients’ nutritional needs when normal feeding is not feasible. This study was designed to explore current practices and barriers to PN from the perspective of pharmacists. Data were collected through semi-structured, face-to-face interviews with pharmacists. The key themes that emerged were knowledge, complications, pharmacists’ roles, and challenges and barriers. The most common educational activities were workshops, board study, undergraduate education, and residency training. The most common complications of PN were fluid and electrolyte abnormalities, infections, and refeeding syndrome. The most common roles of pharmacists were educating patients, calculating PN dosages, monitoring patients, and compounding PN solutions. The most common barriers were shortages of PN components and compounding facilities, inadequate training, and a shortage of experienced staff. In conclusion, this study emphasizes the importance of pharmacists’ roles in PN treatment; however, many barriers make their tasks difficult.
Immune-mediated reproductive failure is increasingly recognized in patients with infertility, particularly those with elevated natural killer (NK) cell activity or other immunological abnormalities. This research note presents clinical experience with immunomodulatory protocols combining Intralipid infusions and low-dose corticosteroids. Intralipid, a soybean oil-based lipid emulsion, is used off-label to downregulate NK cell activity, improve implantation, and enhance pregnancy outcomes, whereas corticosteroids modulate excessive immune responses. The protocols are applied during the preconception period and early pregnancy in selected patients following immunophenotyping of peripheral blood cells. Clinical observations suggest that this combined approach is well tolerated, cost-effective, and potentially beneficial for improving reproductive outcomes in appropriately selected patients with infertility. However, the effectiveness of Intralipid therapy and other therapeutic interventions in reproductive medicine remains controversial, highlighting the need for larger, well-designed randomized controlled trials to clarify their clinical benefits.
The present study investigated consumer awareness, consumption patterns, and home cultivation of microgreens in Northeastern Bulgaria using a questionnaire-based survey of 198 adults. Descriptive statistics, exploratory factor analysis (EFA), and K-means cluster analysis were employed to identify patterns of knowledge, familiarity, and consumption behaviour. The results demonstrated high recognition of microgreens as edible plants and general awareness of their nutritional value, including vitamins, minerals, antioxidants, and fibre. However, actual consumption and home cultivation remained relatively limited. Factor and cluster analyses identified three distinct consumer groups differing in nutritional awareness and familiarity with microgreens, which strongly influenced consumption frequency. Despite this relatively high awareness, microgreens are not yet integrated into everyday dietary practices. The findings highlight the need for improved public information, market availability, and practical guidance to support the wider dietary use of microgreens as functional foods.
The integration of artificial intelligence (AI) into the pharmaceutical sector in Jordan remains limited. This study aimed to measure and analyze changes in pharmacists’ attitudes after the implementation of a targeted educational intervention designed to reduce resistance to AI technology. The study comprised two phases: Phase I, a cross-sectional survey ( N = 901), and Phase II, a one-group pretest–posttest design ( N = 301). Although 75.1% ( n = 677) of the 901 pharmacists reported familiarity with AI, only 41.7% ( n = 376) of the total cohort reported actively using AI. The Phase I results identified the factors significantly associated with technology use as graduation after 2020 (adjusted odds ratio [AOR] = 1.943, p < 0.001), having a postgraduate degree (AOR = 2.402, p = 0.002), and the availability of digital infrastructure in the workplace (AOR = 2.099, p = 0.003). The Phase II intervention results showed a significant immediate reduction in the self-reported fear of job replacement (−45.4%), whereas beliefs regarding the need for human oversight remained essentially unchanged ( p = 0.324). The digital divide among Jordanian pharmacists may be more strongly associated with technological friction—specifically, a lack of digital infrastructure—than with merely generational resistance. However, further research is needed to determine whether these short-term attitudinal shifts translate into long-term changes in practice.
Aim : Over the past decade, nanomedicine has made significant progress in the development of inorganic nanoparticle (iNP)-based drug delivery systems (DDSs). The aim of this narrative review is to summarize the most recent developments in iNP systems, emphasize their advantages as DDSs, and provide detailed commentary on their impact on human health. A systematic search was performed in the PubMed, Scopus, and Web of Science databases for peer-reviewed original research and review articles published between 2020 and 2025. Relevant scientific data on innovative applications of iNPs in cancer therapy were reviewed. The enormous potential of magnetic nanoparticles (NPs), metal–organic frameworks (MOFs), and iNPs used as carriers of small interfering RNAs (siRNAs) as innovative strategies for enhancing antitumor treatment is highlighted. Conclusion : Continuous progress in research strategies for synthesizing iNPs with optimal properties while minimizing adverse effects on living cells is a prerequisite for even greater translational potential of iNP-based DDSs.
The hyperkeratotic stratum corneum is a principal barrier to the efficient topical treatment of psoriasis and limits drug penetration and therapeutic efficacy. In this regard, the aim of this study was to prepare a new topical delivery system containing clobetasol propionate (CP)-encapsulating nanoliposomes dispersed in Carbopol 940 hydrogel and various plant-derived microneedle-like structures for improved topical drug administration. The optimum formula (F2) had a vesicle size of 100 nm, a low polydispersity index (PDI; 0.152), a moderate zeta potential (−16 mV), and high encapsulation efficiencies of 98.8 ± 0.16% by the indirect method and 94.3 ± 0.49% by the direct method. Physicochemical analyses confirmed that CP was successfully incorporated, ensuring the preservation of structural integrity within the engineered nanoliposomal arrangement. The pH, viscosity, and spreadability of the optimized nanoliposomal hydrogel (F2Hb) were all within suitable ranges for the topical application of nanoliposomes. In vitro drug release studies indicated that the optimum nanoliposomal hydrogel formula (F2Hb) provided a sustained release profile; however, when plant-derived microneedle-like structures were incorporated into the nanoliposomal hydrogel (F2HbM), ex vivo skin deposition improved. In an imiquimod-induced mouse model of psoriasis, F2HbM significantly reduced erythema, scaling, and skin thickness and markedly decreased the levels of interleukin (IL)-17A and IL-23. These results indicated that the nanoliposomal hydrogel was an effective strategy for the topical delivery of CP, with sustained drug release and enhanced skin deposition via microneedle-like structures for the treatment of psoriasis.
The management of ocular hypertension and the various forms of glaucoma during pregnancy and lactation represents a significant clinical challenge. The main concerns are related to the selection of an appropriate therapeutic strategy, with special attention paid to the risks associated with treatment for both the mother and the fetus or breastfed infant. There is no universally accepted management protocol for these patients. Owing to the understandable lack of randomized clinical trials in this population, there is currently no officially approved antiglaucoma medication for use during pregnancy or breastfeeding. Selective laser trabeculoplasty is an excellent option for reducing intraocular pressure during pregnancy and lactation, particularly in view of its favorable safety profile. Two clinical cases of patients with ocular hypertension and elevated intraocular pressure who underwent selective laser trabeculoplasty are presented. A sustained and significant reduction in intraocular pressure was achieved. In both cases, the need for antiglaucoma medication was eliminated throughout the follow-up period.
While oral anticoagulants (OACs) are critical for managing thromboembolic diseases, their use carries significant bleeding risks, underscoring the importance of patient comprehension for safety and therapeutic success. Existing tools to measure this knowledge often lack cultural adaptation for Arabic-speaking populations or are restricted solely to vitamin K antagonists. This cross-sectional study aimed to translate, culturally adapt, and psychometrically validate the Oral Anticoagulation Knowledge Tool (AKT) for Arabic-speaking Iraqi patients. The study included 280 adult cardiovascular outpatients in Baghdad (140 prescribed warfarin and 140 prescribed direct oral anticoagulants [DOACs]). Following rigorous forward-backward translation, the adapted tool demonstrated excellent content validity, with a scale content validity index of 0.89, retaining all original items. Principal component analysis confirmed the multidimensional nature of clinical knowledge, extracting eight components from the DOAC cohort and 10 from the warfarin cohort. Educational attainment emerged as the most significant predictor of knowledge scores across both therapeutic modalities ( p = 0.003 for DOACs; p = 0.006 for warfarin). The DOAC scale demonstrated acceptable internal consistency ( α = 0.700), whereas the full warfarin scale exhibited low overall reliability ( α = 0.512), although its specific clinical subdomains showed strong independent reliability ( α ranging from 0.695 to 0.972). Ultimately, the Arabic AKT proved to be a culturally congruent and psychometrically sound instrument when used as a domain-specific formative index for identifying knowledge gaps.
