Quantitative Structure-Property Relationship (QSPR) modelling provides an efficient computational framework for predicting physicochemical properties of drug molecules when experimental data are limited. In this study, we investigate the predictive capability of degree-based topological indices (TIs) derived from SMILES (Simplified Molecular Input Line Entry System) representations for modelling physicochemical properties of anti-alkaptonuria drugs. Nine representative compounds, including Nitisinone, Ascorbic Acid, Ibuprofen, Naproxen, Paracetamol, Tramadol, Methotrexate, Sulfasalazine, and Glucosamine, were analysed using several molecular descriptors such as molecular weight, logP, hydrogen bond donors and acceptors, rotatable bonds, and polar surface area. A total of 58 regression models were developed using Linear Regression (LR) and two machine learning algorithms, Random Forest (RF) and Extreme Gradient Boosting (XGBoost, abbreviated XGB). Model performance was evaluated using Mean Absolute Error (MAE), Mean Squared Error (MSE), Root Mean Squared Error (RMSE), and the coefficient of determination R 2 . The results demonstrate that machine learning models significantly outperform classical regression, with XGB achieving the most accurate and stable predictions for the investigated physicochemical properties. This study introduces a machine learning-driven QSPR framework that integrates SMILES-derived degree-based topological indices with ensemble learning techniques for predicting physicochemical properties of anti-alkaptonuria drugs. The proposed approach demonstrates improved predictive performance on small datasets and highlights the effectiveness of combining graph-theoretic molecular descriptors with advanced machine learning methods.
In a policy environment with constrained access to the medications for opioid use disorder (MOUD), we examined the prevalence and correlates of extra-medical use of these medications among individuals already prescribed MOUD. Among 641 adults in Baltimore participating in the ALIVE cohort study, who self-reported buprenorphine or methadone treatment, we estimated the prevalence of using these same medications outside a formal treatment context ("extra-medical MOUD"). Using logistic regression with generalised estimating equations to account for clustering within individuals, we assess behavioural, sociodemographic, and clinical correlates of extra-medical MOUD use in this population. Across 1325 visits in January 2023-December 2024 (73% aged ≥ 50 years, 68% Black, 64% male), 129 (10%) reported use of extra-medical MOUD. Use of multiple substances (OR 6.05 [95% CI 3.96, 9.23]), injection drug use (6.79 [4.30, 10.70]), any withdrawal sickness (5.51 [3.62, 8.38]) and depressive symptoms (3.90 [2.64, 5.76]) were significantly associated with extra-medical MOUD use. Those engaged in methadone treatment ≥ 6 months had significantly lower odds of extra-medical use (adjusted OR [aOR]: 0.42 [0.22, 0.80]), compared with those newly engaged. By contrast, prescribed buprenorphine dose, but not duration of engagement, was associated with extra-medical use. Among adults receiving legally prescribed or dispensed buprenorphine or methadone, extra-medical use of these same medications was reported at one in every 10 visits. Those with heightened vulnerability to drug-related harms were most likely to use extra-medical MOUD. Findings have implications for policies and practices restricting treatment access.
The One Health approach recognizes that antimicrobial monitoring and regulations must jointly address the risks of antimicrobial resistance in human and animal health for effective strategy and policy to achieve global public health. We operationalize this principle by integrating the World Health Organization's human importance classifications with the World Organization for Animal Health's veterinary classifications to create a hierarchical framework that prioritizes human health. This framework underpins our unique "One Health Score" (OHS), to evaluate regulatory compliance of country-specific drug residue limits with international standards of Codex. Codex, the European Union, and the United States are identified as leaders of establishing maximum residue limits to which other countries defer to. Among pairs with medical classifications, 53% fall under the pairing of Highly Important Antimicrobials (H3) for humans and Veterinary Critically Important Antimicrobials (V1) for animals. The One Health Score is non-negative for at least 50% of countries at each medical importance level. However, 21% of the countries with H3V1 MRLs are laxer than Codex. Drugs with a high market demand in animal agriculture are the most commonly regulated among countries. This suggests drugs used less in food animals may not be adequately regulated currently, despite, in some cases, being highly important for human health. Country officials must balance economic and health priorities when setting or modifying drug residue limits.
Premature atherosclerotic cardiovascular disease (ASCVD) remains a significant challenge in India, despite comparatively lower population-level low-density lipoprotein cholesterol (LDL-C) levels. The Lipid Association of India advocates for aggressive lipid-lowering therapy to achieve an LDL-C target <50 mg/dL in patients with established ASCVD. To provide contemporary data on LDL-C goal attainment in Indian patients with ASCVD. In this largest Indian study to date, 115 cardiologists across India recruited 10,417 patients (9,658 with complete information, mean age 60.7 ± 23.6 years, 7,427 [76.9%] men) with documented coronary artery disease who were on stable lipid-lowering therapy for at least 1 month before their most recent LDL-C measurement. Only directly measured LDL-C was considered. The median treated LDL-C concentration was 66.1 mg/dL (IQR: 49.0-92.0) with only 27.0% (2,603 of 9,658, 95% CI: 26.1%-27.8%) having values ≤50 mg/dL. High-intensity statin therapy was used in 73.0% (7,053 of 9,658, 95% CI: 72.1%-73.9%) of subjects. Combination LDL-C lowering therapy was used in 12.0% (1,155 of 9,658, 95% CI: 10.9%-12.2%) of subjects (8.7% [839 of 9,658, 95% CI: 8.1%-9.3%] receiving 2 drugs, 3.2% [312 of 9,658, 95% CI: 2.9%-3.6%] receiving 3 drugs). Among patients with LDL-C >50 mg/dL, the treating clinicians uptitrated the regimen in only 37.3% (2,552 of 6,833, 95% CI: 36.2%-38.5%) of subjects. This study highlights a major gap in LDL-C control for secondary prevention of ASCVD in India. Despite high-intensity statin use, only one-quarter achieved target levels. Low use of combination therapy and clinician inertia toward treatment intensification remain key concerns, requiring urgent action to improve outcomes in this high-risk population.
Bibliometric analysis is a method for analyzing article data, such as those from books and journals. Pharmacokinetic studies are one way to determine the course of drugs in the body, and the irrational use of drugs, especially antibiotics, will cause antibiotic residues and antimicrobial resistance. To assess the pharmacokinetic research trends of norfloxacin and tylosin in poultry and reptiles, bibliometric analyses focusing on pharmacokinetics and antimicrobial resistance are necessary, in as much as improper dosage can lead to increased antimicrobial resistance, especially due to the frequent antimicrobial exposure in these species and the potential public health implications of emerging resistance. This is the first bibliometric analysis on this combination in poultry and reptiles that has not been previously studied. A bibliometric analysis was performed using keywords such as norfloxacin, tylosin, poultry, reptiles, antibiotic residues, antimicrobial resistance, and their combinations. Keywords were recorded in Google Scholar, Scopus, PubMed, and ResearchGate from 2000 to 2023. Visualizing scientific landscapes using VOSviewer version 1.6.20. After a comprehensive review of the entire text, research articles were screened and filtered. Sixty-one research articles were screened in this study. Our analysis indicates that bibliometric analyses of the pharmacokinetic interactions between norfloxacin and tylosin in poultry and reptiles have been performed over the last two decades. The pharmacokinetics of the combination of norfloxacin and tylosin in poultry and reptiles have shown significant developments over the last two decades.
Rational prescribing is essential for patient safety and cost-effective healthcare. Good prescription writing is important from a treatment, documentation, and medico-legal point of view. The World Health Organization (WHO) prescribing indicators and the National Medical Commission (NMC) guidelines provide standardized benchmarks to evaluate and monitor prescription quality. However, these are mainly applicable to outpatient department (OPD) setups. The high patient volumes, time constraints, and high-pressure, resource-limited environment might alter doctors' prescribing behavior in emergency settings, particularly in developing countries. This study aims to evaluate prescribing practices in a government emergency department using WHO core prescribing indicators and assess prescription completeness against NMC standards. A secondary objective was to evaluate shift-based variation in prescribing quality. This retrospective cross-sectional study analyzed 648 prescriptions collected over one year as part of a quality improvement initiative. WHO prescribing indicators, NMC compliance parameters, and prescription completeness metrics were assessed. Statistical analysis included non-parametric tests, chi-square tests, and multivariate regression models. A total of 1719 drugs were prescribed, with a mean of 2.65 drugs per prescription. Of these, 1115 (64.9%) were prescribed by generic name, and 1500 (87.6%) adhered to the National List of Essential Medicines (NLEM). Antibiotics were prescribed in 42 (6.5%) prescriptions, whereas injections were used in 585 (90.3%) prescriptions. Documentation gaps were significant, with diagnosis recorded in only 55 (8.5%) and complete prescriber identification in just 5 (0.8%) prescriptions. Only 21 (1.2%) drug entries met conventional completeness criteria; it improved to 960 (55.8%) after adjusting for stat-dose prescriptions. Shift-based analysis revealed a significant decline in diagnostic documentation from morning to night shifts, while vital recording remained relatively stable. After adjusting for age, gender, and total medications, night shift was independently associated with higher odds of injection use and lower odds of antibiotic prescribing as compared to morning. Older age and higher total medications were also independent predictors of injection use. Prescribing practices in the emergency department showed significant deviations from WHO indicators and NMC standards, particularly in documentation and injection use. While low antibiotic prescribing reflects cautious antimicrobial use, high injection rates and poor documentation highlight areas for improvement. Shift-based variation suggests an "off-hours effect" influencing clinical decision-making. Targeted interventions, including structured prescription formats, audit-based feedback, and shift-specific strategies, are needed to enhance prescribing quality and patient safety.
The membrane-associated RING-CH (MARCH) family is a type of membrane-localized E3 ubiquitin ligase, which catalyze substrate ubiquitination via their characteristic RING-CH domains. MARCH proteins target their substrates for polyubiquitination of different linkage types and degradation via distinct routes. This review outlines recent advancements about the structural features, subcellular localizations, expression profiles of MARCH proteins and their roles in regulation of physiological processes and diseases, such as immune response, organelle homeostasis and tumorigenesis. Future studies would identify additional targets of the MARCH family and reveal the regulatory networks of MARCH family on substrates, offering an opportunity to target the MARCH family for development of drugs against severe human diseases.
Several randomized controlled trials (RCTs), animal studies, and observational studies have demonstrated the cardioprotective effects of statins, though their effectiveness varies. The observed variability may be attributed to individual differences, patient ages, disparities in statin type and dosage of anthracyclines (ANT) administered, and variations in cancer conditions among patients. Overall, statins play a beneficial role in reducing oxidative stress and inflammation, enhancing tumor sensitivity to chemotherapeutic drugs, improving mitochondrial function in cardiac cells, exerting antiapoptotic effects, and preserving left ventricular ejection fraction (LVEF). Despite these promising findings, the long-term effects of statins remain unclear due to the lack of a standardized protocol. Statins may also cause side effects by depleting essential substances in the body. This limitation underscores the need for further research to assess their long-term impact and establish standardized guidelines for dosing, duration, and potential side effects. The implications of this review highlight the importance of understanding the pleiotropic effects of statins to develop targeted therapies for chemotherapy-induced cardiotoxicity. Additionally, integrating ongoing research into clinical guidelines is essential, ensuring that clinicians carefully consider patient-specific factors when prescribing statins alongside ANT. This present review explores the potential role of statins in mitigating ANT-induced cardiotoxicity, a major complication of chemotherapy that reduces LVEF and leads to heart failure (HF).
Trypanosoma evansi causes surra disease, leading to livestock losses and liver damage. Chemical treatments often result in resistance and side effects, highlighting the need for natural alternatives. Red ginger (Zingiber officinale Roscoe) contains bioactive compounds with antioxidant, anti-inflammatory, and antiparasitic properties. This study evaluated the efficacy of red ginger extract against the Internal transcribed spacer 1 (ITS1) gene expression of T. evansi and liver histopathology in experimentally infected mice (Mus musculus). Male mice were divided into five groups: Healthy Control, Infected Control (IC), Positive Drug Control, and treatment groups receiving red ginger extract at 30, 45, and 60 mg/kg BW. Parasitemia was monitored daily, and parasite load was measured using ITS1-targeted quantitative polymerase chain reaction (ΔΔCq). Liver histopathology was scored for edema, necrosis, hemorrhage, fatty degeneration, and inflammatory infiltration. Survival was analyzed using Kaplan-Meier curves and the log-rank test. Data were analyzed using one-way ANOVA or Kruskal-Wallis test (p < 0.05). Ethanol-extracted red ginger reduced ITS1 gene expression and improved liver histology in a dose-dependent manner. The IC showed hepatocyte degeneration, necrosis, and inflammation, whereas treatment groups exhibited improved hepatocyte structure, reduced inflammation, and normalized sinusoids, especially at 60 mg/kg BW. Survival was highest in the 60 mg/kg BW group. All differences were statistically significant (p < 0.05). Red ginger extract is a promising natural therapeutic agent against T. evansi, effectively reducing ITS1 gene expression, improving liver histopathology, and supporting livestock trypanosomiasis management while reducing reliance on chemical drugs.
Although tachyarrhythmias are associated with thyrotoxicosis, the association with ventricular fibrillation is unknown. This case reports a recurrent ventricular fibrillation with Graves' disease that was successfully treated with an implantable cardioverter defibrillator. A 33-year-old woman presented with ventricular fibrillation cardiac arrest. She was diagnosed with Graves' disease and was taking antithyroid drugs, but her hyperthyroidism was poorly controlled. The patient received intensive care unit care, including extracorporeal membrane oxygenator, ventilator, and renal replacement therapy. Implantable cardioverter defibrillator was implanted for the secondary prevention of ventricular fibrillation. Two months after the procedure, ventricular fibrillation recurred, and an implantable cardioverter defibrillator successfully prevented sudden cardiac death. She maintained a normal sinus rhythm and normal thyroid function after receiving radioactive iodine-131 therapy. Ventricular fibrillation is a rare but fatal manifestation in patients with hyperthyroidism. Implantable cardioverter defibrillator should be considered, especially in patients with poorly controlled hyperthyroidism, for the prevention of sudden cardiac death.
Asthma-chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS) accounts for 15-25% of chronic obstructive airway disease and is linked to frequent exacerbations and excess mortality. Newer glucose-lowering drugs may affect respiratory outcomes, but agent-level and dose-specific effects on ACOS are uncertain. We searched PubMed, Embase, Cochrane CENTRAL, Web of Science, ClinicalTrials.gov, ClinicalKey, ScienceDirect, and ProQuest from inception to April 03, 2026, with an initial search on Dec 12, 2024. Eligible studies were randomised controlled trials in adult participants receiving eligible glucose-lowering therapies and systematically recording ACOS-related, asthma, or COPD events during follow-up. Trials compared dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, sodium-glucose cotransporter 2 (SGLT2) inhibitors, and other eligible antidiabetic regimens against standard care and/or placebo control. Risk ratios (RRs) with 95% CIs were estimated relative to this control group for ACOS, asthma, and COPD outcomes. Heterogeneity was assessed using tau-squared and I 2 statistics, and small-study effects/publication bias were assessed using comparison-adjusted funnel plots and Egger's regression. Outcome was trial-reported ACOS-related respiratory events. This study is registered with PROSPERO, CRD42024626613. Canagliflozin (RR 0.62, 95% CI 0.40-0.97), empagliflozin (0.70, 0.51-0.95), dapagliflozin (0.76, 0.63-0.92), and injectable semaglutide (0.64, 0.49-0.84) were associated with lower ACOS risk than control. Dose-stratified analyses suggested stronger associations for selected regimens, with signals more evident in participants with diabetes. Dapagliflozin was associated with lower asthma risk, whereas canagliflozin, empagliflozin, and injectable semaglutide were associated with lower COPD risk. Saxagliptin was associated with higher asthma risk (2.09, 1.01-4.33). No major heterogeneity, inconsistency, or small-study effects were detected. Respiratory associations of newer glucose-lowering therapies were heterogeneous and agent specific. Selected SGLT2 inhibitors and injectable semaglutide were associated with lower ACOS-related risk, whereas saxagliptin may warrant caution in people prone to asthma. These findings support further prospective evaluation. Taiwan National Science and Technology Council.
Protein arginine methyltransferase 5 (PRMT5), a type II arginine methyltransferase, is overexpressed in several aggressive B-cell malignancies and facilitates cancer cell proliferation. JNJ-64619178, a selective small-molecule inhibitor targeting PRMT5, has previously shown promising preclinical activity across a range of hematological malignancies; however, the clinical activity of JNJ-64619178 monotherapy is limited despite strong target engagement. Therefore, we sought to identify rational combination partners for JNJ-64619178 to achieve improved activity in B-cell malignancies. Using dynamic Bcl-2 homology 3 (BH3) profiling, a functional assay to evaluate the net increase in proapoptotic signaling in response to drugs, we found that JNJ-64619178 increased overall proximity to apoptotic cell death (mitochondrial apoptotic priming) and dependence on B-cell leukemia/lymphoma (BCL)-2 for survival (BCL-2 dependence), particularly in diffuse large B cell lymphoma (DLBCL) and mantle cell lymphoma (MCL) cell lines. In other B-cell non-Hodgkin lymphoma (B-NHL) cell lines that are primarily MCL-1 dependent and less BCL-2 dependent, JNJ-64619178 increased mitochondrial apoptotic priming without shifting anti-apoptotic dependence from MCL-1 to BCL-2. Co-targeting PRMT5 and BCL-2 synergistically induced apoptosis in DLBCL and MCL cell lines that displayed at least partial BCL-2 dependence at baseline, but not in less BCL-2-dependent B-NHL cell lines. Interestingly, JNJ-64619178 upregulated death receptor 4 (DR4) and death receptor 5 (DR5) expression on the cell membrane of B-NHL cell lines, thereby sensitizing them, including the less BCL-2-dependent cell lines, to recombinant TRAIL-induced extrinsic apoptotic cell death. These findings highlight a role of PRMT5 in regulating both intrinsic and extrinsic apoptosis and suggest potential combination partners with PRMT5 inhibitors for potential clinical application in B-NHL.
Multiple cancers overexpress forkhead (FOX) box M1 (FOXM1), a transcription factor (TF) that holds great promise for developing cancer drugs. Herein, through yeast-two-hybrid (Y2H) screening, we obtained a novel FOXM1-targeting peptide M1-NP1, which significantly inhibited the cell cycle and migration of cancer cells. Mechanistically, M1-NP1 bound to the C-terminal region of FOXM1 and disrupted its interactions with the cell cycle-related kinase polo-like kinase 1 (PLK1) and the transcriptional co-activator cyclic adenosine monophosphate (AMP) response element-binding protein (CREB) binding protein (CBP), thus inhibiting FOXM1 transcriptional activities. Additionally, M1-NP1 affected FOXM1 distribution in cells, preventing FOXM1 from infiltrating the nucleus to exert its effects. Furthermore, M1-NP1 treatment in cancer cells downregulated the gene sets of cell cycle phase transition and upregulated the gene sets of cell adhesion. Moreover, M1-NP1's anti-cancer effects were confirmed in wild-type (WT) mice, without any notable toxic or side effects. In addition to its good safety indications, such as the low levels of immunogenicity and hemolysis, M1-NP1 also exhibited a favorable profile regarding stability and distribution in mice. Overall, M1-NP1 targets FOXM1 for cancer therapy.
Coccidiosis caused by Eimeria spp. remains one of the most economically important diseases in poultry production worldwide. The extensive use of chemical anticoccidials has led to increasing drug resistance and concerns regarding residues, highlighting the need for effective and safe natural alternatives. This study aimed to evaluate the anticoccidial efficacy of selected natural plant extracts as alternatives to conventional chemical antiparasitic drugs in broiler chickens experimentally infected with Eimeria spp. Broiler chickens were allocated into four experimental groups: non-infected control, infected untreated control, chemically treated, and plant extract-treated groups. Birds were monitored for growth performance, fecal oocyst shedding, intestinal lesion scores, histopathological changes, hematological parameters, and immunological, biochemical, and antioxidant responses. Plant extract supplementation significantly improved body weight gain and feed conversion ratio, reduced oocyst shedding, and lowered intestinal lesion scores compared with infected untreated birds (p < 0.05). Histopathological examination revealed marked preservation of intestinal architecture in extract-treated birds, comparable to the chemically treated group. Additionally, plant extracts enhanced antioxidant enzyme activities, improved immunoglobulin levels, normalized inflammatory and organ function biomarkers, and restored hematological parameters disrupted by Eimeria infection. The evaluated plant extracts demonstrated pronounced anticoccidial, immunomodulatory, and antioxidant effects, with efficacy comparable to that of chemical anticoccidials. These findings support the potential use of natural plant extracts as safe, effective, and sustainable alternatives for controlling coccidiosis in poultry production.
Neuromuscular blocking agents are widely used in veterinary anesthesia to facilitate tracheal intubation and provide optimal surgical conditions. Quantitative neuromuscular monitoring enables accurate evaluation of neuromuscular effects while ensuring cardiovascular safety in anesthetized dogs. This study aimed to quantify the neuromuscular effects, therapeutic effectiveness, and cardiovascular safety of rocuronium and atracurium during quantitative neuromuscular monitoring of dogs under ambulatory anesthesia. A total of 18 healthy adult dogs were randomly divided into two groups. One group received 0.6 mg/kg IV of rocuronium, and the other received 0.5 mg/kg IV of atracurium after the induction of isoflurane anesthesia, with each group consisting of nine dogs. Neuromuscular transmission was quantified using calibrated train-of-four (TOF) acceleromyography. Onset time, duration of action, and recovery time to a TOF ratio ≥ 0.9 were measured concurrently with continuous monitoring of heart rate, mean arterial pressure, and oxygen saturation. The use of rocuronium resulted in a significantly faster onset of neuromuscular block compared with atracurium (p < 0.001), enabling rapid tracheal intubation. No significant differences were found between the two groups regarding the duration of action and recovery time. During the anesthesia period, cardiovascular parameters remained stable and comparable between the groups, and only one dog in the atracurium group experienced a minor, transient adverse effect. The results suggest that both drugs are potent and do not harm dogs. In addition, rocuronium is a better option for quick procedures, whereas atracurium can be used in situations where it is not anticipated that the patient will be able to respond to reversal agents or has compromised organ function, due to its predictably less discomfort during the recovery phase.
Novel psychoactive substances (NPS) are synthetic compounds designed to mimic illicit drugs while circumventing international drug regulations. Commonly marketed as "research chemicals" or "legal highs", these substances remain poorly understood, with limited evidence regarding their pharmacology, risks, and therapeutic potential. Current drug policies often place NPS in the strictest legal schedules, restricting the clinical and pharmacological research needed to assess both harms and possible medical benefits. This paper advocates for a public health-oriented regulatory framework that balances harm reduction with controlled scientific access. Existing clinical evidence indicates that some NPS present significant risks, whereas others may possess therapeutic value. To address this complexity, an evidence-based four-stage scheduling framework is proposed: Early Surveillance to identify emerging substances and harms; Provisional Scheduling to permit access to regulated research; Controlled Research to investigate pharmacology, safety, subjective and neurocognitive effects, abuse liability, and therapeutic potential; and Reclassification based on integrated clinical, toxicological, and public health evidence. This approach would reduce research barriers and support more adaptive, evidence-based regulation and more balanced drug policies. None.
Potentially inappropriate medications (PIMs), are common among residents of long-term care institutions (LTCIs) and may contribute to cognitive impairment (CIm). STOPPCog criteria, developed in 2025, support the identification of PIMs relevant to cognition and accuracy of dementia treatment. The study aimed to identify PIMs according to the STOPPCog criteria among residents of long-term care institutions in Poland, and to assess the association between CIm and exposure to specific drug classes. This is a multicenter cross-sectional study in four LTCIs. Medication lists were reviewed using STOPPCog criteria and anticholinergic burden scales. Cognitive status was assessed with the Mini-Mental State Examination (MMSE), and CIm was defined using a conventional cut-off. We compared exposure frequencies between residents with and without CIm and explored factors associated with MMSE using regression models adjusted for key demographic and clinical variables and facility effects. Of 204 residents, 133 (65.2%) had at least one STOPPCog-listed medication on their medication list. Drugs with anticholinergic burden (ACB) (54.9%), especially one subgroup - antipsychotics (39.2%), were most frequently used within the study sample. Antipsychotics were the only drug class significantly associated with CIm independently of sex, age, comorbidity burden, and facility (p < 0.001). The majority of residents with a previous diagnosis of dementia in their medical records and consequently dementia-specific pharmacotherapy had severe CIm. There is a high prevalence of PIMs among LTCIs residents. Antipsychotic deprescribing and early diagnosis of CIm should be further evaluated in future prospective studies and clinical practice.
Persistent microbial biofilm infections remain a major obstacle to effective antimicrobial therapy due to restricted drug diffusion, metabolic heterogeneity, and the presence of tolerant bacterial subpopulations. In device-associated infections, biofilms substantially reduce antibiotic efficacy and contribute to chronic relapse despite adequate systemic exposure. Although nanocarrier-based delivery systems have been widely investigated, many formulations remain empirically developed with insufficient consideration of biofilm-specific physicochemical and biological barriers. This review examines surfactant-engineered niosomal antibiotic systems from a rational design perspective. Key formulation parameters, including surfactant type, hydrophile-lipophile balance (HLB), cholesterol content, surface charge, and microenvironment-responsive behavior, critically influence bilayer rigidity, permeability, encapsulation efficiency, intrabiofilm transport, and release kinetics. In particular, electrostatic interactions with the negatively charged extracellular polymeric substance (EPS) matrix and pH-responsive destabilization strategies are discussed as important determinants of localized antibiotic delivery within heterogeneous biofilm environments. Despite promising antibiofilm activity in vitro, translational progress remains limited by variability in formulation characterization, insufficient in vivo validation, and incomplete alignment between carrier responsiveness and biofilm microenvironmental conditions. By integrating insights from pharmaceutics, materials science, and microbial pathophysiology, this review proposes a structured framework for the rational design of surfactant-engineered niosomes and highlights key considerations for advancing antibiofilm nanomedicine.
Wound healing involves a sequential transition from inflammation to proliferation, requiring a balanced immune response. The disruption of this balance can impair repair. Origanum vulgare (oregano) has been reported to exert immunomodulatory properties; however, evidence regarding its influence on IL-10 and Vascular Endothelial Growth Factor (VEGF) expression in excisional wound healing remains limited. This study aimed to evaluate the effect of topical oregano extract ointment on the expression of IL-10 and VEGF in a rat excisional wound model. Twenty-four male white rats were randomly assigned to four groups (n = 6 per group): vehicle control and oregano extract ointment at concentrations of 3%, 6%, and 9%. A standardized 5-mm full-thickness excisional wound was created on the dorsal skin. Treatments were applied topically twice daily for 14 days. On day 14, skin tissues were harvested for immunohistochemical analysis of IL-10 and VEGF expression. Immunohistochemical analysis was performed using Immunohistochemistry Profiler, and statistical analysis was conducted using one-way ANOVA followed by Tukey's post hoc test (p < 0.05). IL-10 expression showed an upward trend in the oregano-treated groups compared with the vehicle control; however, the differences did not reach statistical significance. In contrast, VEGF expression was significantly increased in the 6% oregano extract group compared with the vehicle control (p < 0.01), while the 3% and 9% groups demonstrated non-significant increases. No significant differences were observed among the oregano-treated groups. Oregano extract modulated the expression of molecular markers associated with wound healing, with the 6% concentration significantly increasing VEGF expression. IL-10 showed a non-significant upward trend across the treatment groups. These results suggest that oregano extract may support pathways involved in tissue repair, with 6% representing a potentially optimal concentration under the conditions of this study.
The treatment of wounds associated with diabetes is among the common issues encountered in veterinary healthcare. This research endeavor sought to prepare and evaluate the impact of the composition of Boswellia serrata extract (BSE) and Trigonella foenum-graecum seed extract (TFGE) on the healing of induced diabetic wounds in rats. Thirty-two clinically healthy adult male rats, aged 6-8 months and weighing 280 ± 20 g, were used in this study. After partial pancreatectomy, 2 equal groups (n = 16) were randomly selected among the 32 experimental animals and exposed to a full-thickness excisional wound. Group Ι, represented control, was treated with the topical application of penicillin-streptomycin antibiotic, and group II was treated with ointment prepared from 20% BSE and 10% TFGE. Each group was treated daily for 21 days. Macroscopic analysis exhibited significant superiority (p < 0.05) of wounds in the treated group compared to the control group at the 7th, 14th, and 21st day. The histopathological findings of the treated group (GII) revealed accelerated revascularization, modulation of inflammatory response, enhancement of collagen fiber formation and maturation, regeneration of epidermal tissue, and hair follicles with improved reepithelialization. Gene expression values showed significantly (p < 0.05) upregulation of Vascular Endothelial Growth Factor and Transforming Growth Factor beta 1 and downregulation of tumor necrosis factor-α on days 3, 7, 14, and 21 post-wound treatment, in contrast to the wounds of the control group (GI). Topical application of the Boswellia serrata and T. foenum-graecum seed extracts substantially enhanced excisional wound healing in diabetic animals.