Search Results (9,980)

Background/Objectives: Curcumin (CUR) has shown promising potential as a wound-healing agent for diabetic wounds; however, its efficacy is hindered by poor aqueous solubility and limited skin permeability. To overcome these limitations, CUR was loaded into myrrh oil-based nanoemulsions (NEs). Methods: The NEs were optimized using a three-factor two-level D-optimal mixture design, and characterized for droplet size, polydispersity index, and zeta potential. The optimized NE was subjected to various stability testing and incorporated into a gel base containing insulin (INS) to form CUR-INS nanoemulgel (CUR-INS-NEG). The antibacterial efficacy of CUR-INS-NEG was tested against various bacterial strains, while its wound-healing effects were evaluated in a diabetic rat wound model. Results: The surfactant/co-surfactant concentration had a greater influence on the NE properties than the oil and aqueous phase concentrations. The optimal NE had a droplet size of 155.2 ± 0.8 nm, a polydispersity index of 0.28, and a zeta potential of −31.4 ± 0.8 mV. It demonstrated sustained drug release, with further release control upon incorporation into the gel base. CUR-INS-NEG demonstrated higher in vitro antibacterial efficacy compared with blank NEG, CUR gel, and INS gel. It also showed 2- and 4-fold reduction in the MIC against S. aureus and E. coli, respectively, compared with CUR gel. In a diabetic wound model, CUR-INS-NEG outperformed both CUR gel and INS gel by enhancing anti-inflammatory and antioxidant effects, as well as collagen deposition and endothelial cell proliferation. Conclusions: The CUR-INS-NEG emerges as an effective system for diabetic wound management, delivering complementary anti-inflammatory, antioxidant, and tissue-regenerative effects of myrrh oil, CUR, and INS. Full article

Human activities inevitably affect natural ecosystems, the impact of which most often refers to negative factors resulting in the accumulation of toxic elements in environmental components. This study quantified the presence of 12 toxic elements (Cd, Co, Cr, Cu, Hg, Fe, Mn, Ni, Pb, Zn, As, and Se) in water, soil, and six melliferous plant species across the Republic of Croatia. Sampling sites were classified into four groups according to the dominant anthropogenic impact: agricultural areas, urban and traffic-affected zones, industrial vicinities, and forested hill regions. The results demonstrate the transfer of toxic elements from abiotic matrices into plants, indicating their potential as bioaccumulators. Soil contamination with toxic metals was identified as a relevant ecological risk factor, while contamination of melliferous plants highlights potential implications for human health through the production of honeybee-derived products. Element concentrations in water and soil were determined using three atomic absorption spectrometry techniques (FAAS, GFAAS, and CVAAS), whereas concentrations in floral samples of melliferous plants were measured using inductively coupled plasma mass spectrometry (ICP MS). The obtained results were interpreted in relation to natural background levels and the current national legislation. Anthropogenic impacts were further evaluated using environmental quality indices and bioaccumulation factors, revealing site-specific contamination patterns of both natural and anthropogenic origin. Full article

Background/Objectives: The aim of this study was to clarify the antimicrobial susceptibility and distribution characteristics of Mycoplasma pneumoniae (M. pneumoniae, MP) collected from children in Beijing, China, from 2017 to 2025. Methods: A total of 197 MP isolates were analyzed. Mutations in macrolide-resistant loci of MP strains were detected via real-time fluorescent quantitative polymerase chain reactions. We used the broth microdilution method to determine the minimum inhibitory concentrations (MICs) of erythromycin, azithromycin, tetracycline, levofloxacin, and moxifloxacin against these isolates. The distribution characteristics of MIC values were further analyzed according to the isolates’ collection year, epidemic phase (low epidemic phase, epidemic initiation phase, ultra-low epidemic phase, outbreak phase, and epidemic recovery phase), and the corresponding patient age group (<3 years, 3–6 years, and ≥6 years). Results: All 197 isolates were found to be resistant to erythromycin and azithromycin, with a resistance rate of 100%. In contrast, the strains remained susceptible to tetracycline, levofloxacin and moxifloxacin. The highest resistance rate was 100% for macrolides. The MIC₉₀ values were 1024 μg/mL for erythromycin, 256 μg/mL for azithromycin, 0.5 μg/mL for tetracycline, 1 μg/mL for levofloxacin, and 0.125 μg/mL for moxifloxacin, respectively. Distinct differences in MIC distributions of erythromycin and azithromycin were observed across collection years, epidemic phases, and age groups. Conclusions: The resistance of MP to macrolides in children is closely associated with the epidemic intensity and age of the patient. Erythromycin is no longer suitable as an empirical therapy for MP infections during epidemic periods, whereas azithromycin can be cautiously administered in young children according to age stratification and MIC detection results. Meanwhile, it is imperative to strengthen the prevention and control of cluster MP infections during epidemic phases to reduce the transmission of drug-resistant MP strains. Full article

Background: Huafeng Dan (HFD) is a traditional famous medicine from Guizhou Province, commonly used for the treatment of stroke-induced hemiplegia and epilepsy. Yaomu is a key component and serves as the sovereign herb in the formula. Most of the components of Yaomu are toxic Chinese herbal medicines. Traditional fermentation processing methods are required to reduce its toxicity. Purpose: Current studies have not yet systematically analyzed the chemical constituents before and after fermentation. Meanwhile, there is a lack of safety evaluation before and after the fermentation of Yaomu, which can provide a basis for safe clinical medication. Method: Chemical constituents of Yaomu before and after processing were analyzed using UHPLC-Q/TOF-MS to compare compositional changes induced by fermentation. To further screen potential toxic components, representative compounds were selected from these differential compounds based on statistical indicators (such as VIP value), low cost and easy availability, as well as criteria from the literature, and the content changes before and after fermentation were investigated. In vitro toxicity was evaluated using a microfluidic liver organ-on-a-chip model to assess the toxic effects of Yaomu extracts before and after fermentation. Results: Studies have shown that in both positive and negative ionization modes, a total of 361 compounds were annotated in unfermented Yaomu. After fermentation, a total of 350 compounds were annotated. Multivariate statistical analysis revealed significant differences in the chemical composition of Yaomu before and after fermentation. Quantitative analysis demonstrated that the levels of diester-type diterpenoid alkaloids were significantly reduced after fermentation, accompanied by concurrent decreases in lysophosphatidylcholine (LPC) species, compared with unfermented Yaomu. In contrast, the concentrations of amino alcohol-type diterpenoid alkaloids were significantly increased. The microfluidic liver organ-on-a-chip results demonstrated that the post-fermentation extract caused significantly attenuated impairment of hepatocellular function and viability. The in vitro toxicity findings showed good concordance. Full article

Background: Gaucher disease (GD) is a lysosomal storage disorder caused by deficiency of β-glucocerebrosidase, leading to accumulation of glucocerebroside in lysosomes. Type 1 GD is most commonly associated with the N370S mutation and lacks neurological involvement, whereas the neuronopathic forms (types 2 and 3), frequently linked to L444P homozygosity, present with progressive neurological symptoms. Enzyme replacement therapy (ERT) effectively treats visceral manifestations but does not cross the blood–brain barrier and, therefore, does not improve neurological outcomes. Ambroxol, a plant-derived mucolytic agent, has been shown to act as a pharmacological chaperone capable of increasing residual enzyme activity and crossing into the central nervous system, with reports suggesting neurological benefit in L444P homozygotes. Methods: We evaluated 13 patients with type 3 GD (L444P/L444P homozygotes) who received ambroxol at 10 mg/kg/day for one year as part of a clinical trial. All participants had been on long-term ERT with stable biomarker levels (chitotriosidase, glucosylsphingosine [Lyso-GL1]) and hematological parameters. Neurological symptoms were assessed using the modified Severity Scoring Tool (mSST). Biomarkers and hematologic indices were monitored throughout the study. Results: Ambroxol treatment resulted in a reduction in severity or complete resolution of selected neurological symptoms in several patients. Conclusions: In patients with type 3 GD receiving stable ERT, ambroxol demonstrated beneficial effects on neurological symptom expression. Some improvement was observed in biomarkers; the activity of chitotrosidase and concentration of lyso-Gl1 decreased. These findings support the therapeutic potential of ambroxol as an adjunctive treatment for neuronopathic Gaucher disease. Full article

Background/Objectives: Medicinal plants are widely investigated due to their rich content of biologically active secondary metabolites with potential therapeutic applications. This study aimed to investigate the phytochemical profile and antioxidant activity of extracts with different polarities obtained from Justicia thunbergioides (Lindau) Leonard (Acanthaceae). Methods: Phytochemical screening was initially performed through qualitative analysis, followed by fractionation and characterization of dichloromethane and methanolic extracts using thin-layer chromatography (TLC) and gas chromatography–mass spectrometry (GC–MS). Antioxidant activity was evaluated using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay and electrochemical techniques. Results: GC–MS analysis of the dichloromethane extract revealed a chemically diverse composition, including compounds such as spathulenol, vitamin E, sesamin, squalene, and β-sitosterol, which are widely reported in the literature for their antioxidant and bioactive properties. The methanolic extract exhibited a distinct chemical profile, with a predominance of phenolic and redox-active compounds. DPPH assays demonstrated that the methanolic extract showed the highest radical scavenging capacity in a concentration-dependent manner, whereas the dichloromethane and hexane extracts required higher concentrations to achieve moderate antioxidant effects. Electrochemical analyses indicated that the methanolic extract is rich in electroactive metabolites capable of partially reversible electron transfer, consistent with its enhanced antioxidant performance. Conclusions: Collectively, these findings highlight the antioxidant efficacy of the polar extracts from J. thunbergioides and contribute to a better understanding of the bioactivity of their phytochemical constituents. Full article

Background/Objectives: Spontaneous intracerebral hemorrhage (sICH) is a particularly severe subtype of stroke, characterized by high rates of mortality and long-term disability, for which robust prognostic markers are still lacking. The aim of this study was to assess the relationship of the ICH score, the National Institutes of Health Stroke Scale (NIHSS) score, and serum high-sensitivity cardiac troponin I (hs-cTnI) levels with 30-day mortality in patients with sICH. Methods: We conducted a prospective observational cohort study enrolling 100 consecutive patients diagnosed with sICH based on neuroimaging findings. Demographic data, clinical parameters, neuroimaging findings, and serum hs-cTnI levels were collected on admission. Subsequently, the ICH score, its individual components, and the NIHSS score were assessed. Results: Patients who died were older and had significantly higher ICH and NIHSS scores, lower Glasgow Coma Scale (GCS) scores, larger hematoma volumes, more frequent intraventricular hemorrhage (IVH), and elevated hs-cTnI levels compared to survivors. Serum hs-cTnI concentrations were significantly correlated with ICH and NIHSS scores, lower GCS scores, larger hematoma volumes, and the presence of IVH. On univariate logistic regression, higher ICH score, NIHSS score, and hs-cTnI level were associated with mortality, whereas multivariate analysis identified the GCS score, hematoma volume, and IVH score as significant independent factors related to fatal outcome. Conclusions: Individual components of the ICH score may provide useful information on outcomes in patients with sICH. Higher serum hs-cTnI levels were associated with 30-day mortality but were not independent predictors. These markers may assist in patient monitoring and support established clinical procedures in therapeutic decision-making. Nevertheless, larger multicenter studies are needed to further clarify their clinical implications in sICH management. Full article

Background/Objectives: Tafamidis, a transthyretin kinetic stabilizer, increases circulating transthyretin levels in treated patients. While this effect is well documented, its underlying mechanism remains incompletely understood. This study aimed to evaluate the performance of physiologically based pharmacokinetic (PBPK) model performance and to calibrate a hypothesis-consistent quantitative systems pharmacology (QSP) model of tafamidis and transthyretin dynamics to explore mechanistic hypotheses underlying the clinically observed increase in circulating transthyretin and the associated dose–response relationship. The PBPK model constitutes the primary framework, while the coupled QSP component illustrates how tafamidis exposure predictions can be used to evaluate mechanistic hypotheses of TTR turnover. Methods: A PBPK–QSP model was constructed in Simcyp (V23) using LUA-based modules. The PBPK part was parameterized from the literature and validated against data from therapeutic single-dose, therapeutic multiple-dose, and supratherapeutic dose clinical studies. The QSP part of the model describes tafamidis–TTR binding kinetics, stabilization, and clearance of bound complexes. Simulations were performed in thirty virtual healthy male subjects aged 30–40 years, incorporating physiological variability in baseline TTR concentrations. Results: Mean predicted versus observed ratios of tafamidis AUC and $C_{max}$ values were within a 1.3-fold range across validation studies. The integrated model reproduced the clinically reported 33% increase in TTR concentration through a calibrated clearance-scaling factor. It supports the hypothesis that reduced clearance of tafamidis-bound TTR may explain the observed effect without modifying TTR synthesis. Dose-sensitivity simulations indicated that patients with low baseline TTR may achieve adequate stabilization at reduced doses, while those with higher baseline TTR concentration may require higher doses. Conclusions: The developed PBPK–QSP model not only reproduces tafamidis pharmacokinetics and TTR responses but also proposes a plausible mechanistic hypothesis consistent with clearance modulation of stabilized TTR contributing to the clinical effect. Full article

Background/Objectives: This study investigated the effect of the consumption of carnosine-enriched chicken meat on endothelium-dependent and independent microvascular reactivity and inflammatory mediators in patients with chronic coronary syndrome (CCS). Materials and Methods: In total, 38 CCS participants were randomized to two groups: the Control group (N = 19), who consumed regular chicken meat, and the Carnosine group (N = 19), who consumed carnosine-enriched chicken meat for 3 weeks. Skin microvascular reactivity in response to vascular occlusion (PORH), acetylcholine (ACh ID), sodium nitroprusside (SNP ID), and local thermal hyperemia (LTH) was measured. Arterial blood pressure (BP), heart rate (HR), biochemical parameters, anti- and proinflammatory cytokine levels, and markers of oxidative stress were assessed before and after the intervention. Results: The consumption of carnosine-enriched chicken meat improved endothelium-dependent (PORH, LTH) and endothelium-independent vasodilation (SNP ID). Systolic BP (SBP), diastolic BP (DBP), and mean BP (MAP), as well as serum concentrations of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and endoglin, decreased from the initial measurements. Conclusion: The consumption of carnosine-enriched chicken meat enhances microvascular endothelium-dependent and independent vasodilatation. Patients with CCS can benefit from carnosine-enriched chicken meat consumption through improved hemodynamic parameters, reduced inflammation, and enhanced microvascular relaxation. Full article

Background/Objectives: Bacterial conjunctivitis is a common ocular infection requiring prompt treatment, particularly in vulnerable patients, and may influence perioperative outcomes. This study aimed to characterize conjunctival bacterial isolates phenotypically and genotypically, to evaluate their biofilm-forming capacity, and to investigate the relationship between resistance gene carriage, resistance phenotypes, and biofilm-associated antimicrobial resistance (AMR). Methods: A prospective, single-center, cross-sectional study was conducted on bacterial isolates from conjunctival samples of patients examined in an ophthalmology department. Antimicrobial susceptibility testing (AST) was performed to determine the minimum inhibitory concentrations (MICs). Resistance genes were detected by quantitative PCR. Biofilm-forming capacity was assessed using the microtiter plate assay, and biofilm susceptibility to amikacin (AK) and levofloxacin (LEV) was evaluated using a biofilm susceptibility assay. Results: A total of 78 isolates were analyzed; Gram-positive cocci prevailed (GPC, 84.6%), being significantly more frequent than Gram-negative bacilli (GNB, p < 0.001). Among GPC, 65.2% were multidrug-resistant, with Staphylococcus epidermidis emerging as the most frequent species (p < 0.001). Resistance gene carriage was detected in 33.3% of GNB. Strong biofilm formation was observed in 22.7% of GPC versus 58.3% of GNB. It should be noted that the relatively small number of GNB may limit the statistical robustness of comparisons between Gram-positive and Gram-negative groups. A statistically significant association between resistance genes and biofilm capacity was found only in Staphylococcus aureus (p = 0.027). Biofilm-embedded bacteria showed increased antimicrobial tolerance, particularly for AK in S. aureus and for both AK and LEV in S. epidermidis (p < 0.001). Conclusions: The prevalence of multidrug-resistant conjunctival isolates and their biofilm-forming capacity highlights the clinical importance of biofilm-related resistance and support integrating AMR profiling with biofilm assessment to optimize empirical therapy in bacterial conjunctivitis. Full article

Background: High-density lipoproteins (HDL) exert protective effects on the endothelium, which are impaired in type 2 diabetes (T2D). Although monocyte-derived multipotential cells (MOMCs) can be differentiated into the endothelial lineage, it remains unclear whether HDL glycation, size, and composition could affect MOMCs differentiation. Methods: Twenty normoglycemic (49 years, 35% male), 20 prediabetic (52 years, 35% male), and 20 newly diagnosed T2D participants (51 years, 50% male) were recruited. HDL were isolated from each study group. The size, composition, and early, intermediate, or advanced glycation products of HDL were determined. CD14+ MOMCs were isolated from healthy volunteers and incubated with HDL from each group. Endothelial phenotypic expression was assessed by CD14⁺/KDR⁺ expression. Results: Compared with normoglycemic and prediabetic individuals, T2D patients had higher concentrations of early (4.4, 4.6, vs. 5.2 µmol/mg of protein, respectively; p = 0.049) and advanced (7.7, 8.7, vs. 14.3 µg-BSA-AGEs/mg of protein, respectively; p < 0.02) glycation products in HDL. HDL composition was similar among groups. The CD14+/KDR+ expression in MOMCs incubated with HDL from T2D patients was lower than that observed in prediabetes and normoglycemic individuals (46% vs. 52% and 61%, respectively; p = 0.002). Advanced glycation end products in HDL inversely correlated with CD14+/KDR+ cells (r = −0.418, p = 0.002), adjusting for other HDL characteristics. Conclusions: In T2D patients, increased HDL-advanced glycation impairs the endothelial phenotypic expression of MOMCs, independently of other HDL characteristics. Since advanced glycation leads to greater biological damage, these findings highlight the importance of preserving HDL integrity in T2D patients to support endothelial repair and potentially delay vascular complications. Full article

Background/Objectives: The widespread use of mupirocin and fusidic acid for the treatment and decolonization of Staphylococcus aureus (SA) skin infections has led to a rapid emergence of resistant strains, limiting the effectiveness of the few topical agents currently available for clinical use. Methods: In this study, we evaluate Fe(tropo)₃, a neutral and lipophilic iron(III)–tropolone complex, as a non-antibiotic topical antimicrobial candidate for the management of drug-resistant SA skin and soft tissue infections. Results: Fe(tropo)₃ exhibits potent in vitro activity against methicillin-susceptible SA, methicillin-resistant SA (MRSA), vancomycin-intermediate SA, and strains with high-level resistance to mupirocin and fusidate, with minimum inhibitory concentrations of 2 µg/mL across all tested isolates. The compound effectively penetrates bacterial cells, induces intracellular iron accumulation, and triggers dose-dependent reactive oxygen species generation, resulting in rapid bacterial killing and significant antibiofilm activity. Importantly, Fe(tropo)₃ shows a slower development of resistance compared with ciprofloxacin and displays synergistic activity with oxacillin against MRSA. When formulated as a 1% topical ointment, Fe(tropo)₃ significantly reduces bacterial burden in a murine excisional wound infection model, achieving a 98% ± 1% reduction in SA load without detectable hemolysis or skin irritation. Conclusions: These pilot study results support Fe(tropo)₃ as a clinically relevant, mechanism-distinct topical antimicrobial with potential utility in settings where resistance to existing topical antibiotics compromises standard care. Full article

Background/Objectives: Species of the Sporothrix genus were used as a biological model to identify potential antifungal compounds within the NIH Clinical Collection library. Methods: A total of 707 compounds were screened for antifungal activity using in vitro susceptibility assays. Compounds exhibiting significant inhibitory effects (growth inhibitions greater than 80%) were further evaluated by determining their minimum inhibitory concentrations (MICs). As cerivastatin demonstrated the highest activity after itraconazole, it was selected for further evaluation, either alone or in combination with itraconazole, using susceptibility assays, electron microscopy, and flow cytometry analyses. Results: Among the screened compounds, twenty-six showed significant inhibition of yeast growth (≥80%). Compounds with previously reported antifungal activity or not used as oral treatment were excluded from further analysis. MIC determination of eleven selected compounds revealed that cerivastatin inhibited the growth of Sporothrix brasiliensis, Sporothrix schenckii, and Sporothrix globosa at concentrations of 1.25 µM and 0.6 µM. Combination treatment with cerivastatin and itraconazole resulted in greater inhibition of Sporothrix growth than either agent alone. Flow cytometry and microscopic analyses revealed more pronounced morphophysiological alterations in yeast cells following combination treatment. Conclusions: These findings highlight the potential of cerivastatin as an antifungal agent when used in combination with itraconazole. Furthermore, the chemical scaffold of cerivastatin warrants further investigation as a basis for the development of novel statins with antifungal activity. Full article

Background/Objectives: The multifaceted concept of body image (BI) refers to an individual’s attitudes and impressions of their body. Negative BI is associated with a number of harmful health consequences, including obesity, eating disorders, and symptoms of sadness. The contemporary digital era, marked by the dominance of platforms, has brought about a considerable transformation in the landscape of BI issues. This study’s goal is to compile and assess the connections between social media (SM) use, body weight, and BI in adult populations. Methods: This is a narrative review that comprehensively searches across multiple academic databases, such as PubMed, Medline, Scopus, Web of Science, and Google Scholar. Studies that used SM (online blogs, microblogs, content communities, or social networking sites) for engagement (e.g., sharing, commenting, liking) or image-related activities (e.g., viewing, posting, or engaging with images) with healthy adults (aged 18–70 years) of any body mass index (BMI kg/m²) met the inclusion criteria. Included were observational and experimental studies that examined habitual SM use. Only peer-reviewed works published in English between 2015 and 2025 met the search criteria. Results: The currently available findings suggest that obese people are more dissatisfied with their bodies than people of normal weight, and obese women are more dissatisfied with their bodies than their peers of normal weight. Furthermore, experimental studies have demonstrated that immediate BI is adversely affected by acute exposure to idealized social media photographs. Conclusions: Policies should support specialized training that emphasizes a holistic approach to health and puts functionality and health above attractiveness. This training is crucial for dispelling weight-related stigmas and enabling healthcare providers to offer compassionate treatment that supports mental and physical health. Future research must concentrate on internalization and social pressure or reinforcement because these subjects have not gotten as much emphasis in prior studies. Such mechanism research could help better contextualize the role of recently introduced SM items. Full article

Background: Valproic acid (VPA) poisoning has a dynamic clinical course and may require extracorporeal toxin removal (ECTR) in severe cases. Intermittent hemodialysis is the preferred ECTR technique; however, clinical experience with expanded hemodialysis (HDx) using medium cut-off (MCO) membranes in acute VPA intoxication is scarce. We describe a case of severe VPA poisoning managed with intermittent HDx and outline the clinical rationale and kinetic response. Case Report: A 54-year-old woman presented to the emergency department after accidental presumably ingesting approximately 4 g of VPA, with depressed consciousness (Glasgow Coma Scale 7) and metabolic acidosis (pH 7.10, HCO₃⁻ 13 mmol/L, PCO₂ 50 mmHg, lactate 2.8 mmol/L, ionized calcium 0.8 mmol/L, elevated anion gap). Initial plasma VPA was 262.99 µg/mL, ammonia was 14 µmol/L, and cranial computed tomography showed no acute abnormalities. ECTR was initiated in the intensive care unit as intermittent HDx using an MCO dialyzer for 4 h. Serial VPA concentrations were obtained before treatment, at 2 h, and at the end of the session to guide real-time prescription adjustment, with an increase in blood flow from 200 to 230 mL/min. Results: VPA decreased from 262.99 µg/mL pre-HD to 141.48 µg/mL at 2 h (46.2% reduction) and 97.81 µg/mL at 4 h (62.8% reduction), with clear improvement in the level of consciousness. A mild post-dialysis rebound was observed (100.07 µg/mL at 14 h). The patient recovered without additional ECTR and was discharged with normalized VPA levels on follow-up. Conclusions: In this patient, intermittent HDx with an MCO membrane was feasible, well tolerated, and associated with rapid VPA clearance and neurological recovery. Serial drug monitoring enabled bedside optimization of the dialysis prescription and post-treatment evaluation. A single HDx session was sufficient, and VPA therapy was safely reintroduced under close monitoring. Full article