Abstract Density functional theory (DFT) calculations were performed to investigate the electronic effects of C6 substitution on the nicotinamide (NA) scaffold. Geometry optimizations, frontier molecular orbital analysis, conceptual DFT descriptors, and molecular electrostatic potential (MEP) analyses were employed to establish structure–property relationships for selected electron-donating (CH 3 and NH 2 ) and electron-withdrawing (NO 2 ) substituents. The electronic properties of NA were strongly influenced by substituent character. The weak electron-donating CH 3 group induced only minor changes relative to the parent molecule, whereas the NH 2 and NO 2 substituents produced noticeable variations in frontier orbital energies, dipole moments, and charge distribution. Among the investigated derivatives, the NO 2 -substituted system exhibited the smallest HOMO–LUMO gap, the highest dipole moment, and the highest electrophilicity, indicating enhanced charge separation and electron-accepting ability. Qualitative MEP analysis, further supported by the molecular polarity index (MPI), confirmed substituent-dependent redistribution of electrostatic potential across the molecular surface. Overall, the combined analyses demonstrate that C6 substitution provides a systematic approach for tuning the electronic structure of nicotinamide and establish consistent structure–property relationships that may facilitate the rational design of related functional derivatives.
Dermatological fungal infections represent a major global health concern, often exacerbated by the limitations of conventional antifungal therapies, including poor skin penetration, rapid drug clearance, and uncontrolled release. Ketoconazole, a widely used antifungal agent, requires advanced delivery strategies to enhance its therapeutic efficacy and patient outcomes. Nanogels, owing to their nanoscale dimensions, high water content, and tunable release profiles, have emerged as promising carriers for topical drug delivery. This study reports the development and evaluation of a Ketoconazole-loaded sodium alginate nanogel designed to overcome these therapeutic challenges. A nanogel formulation was prepared using 2 % sodium alginate and 2 % Ketoconazole, stabilized with polyethylene glycol (PEG). The formulation’s physicochemical properties, including particle size, polydispersity index (PDI), and zeta potential, were characterized using a Malvern Zetasizer, while morphology was assessed via Transmission Electron Microscopy (TEM). Drug release was evaluated using the diffusion membrane method, and antifungal efficacy was tested against Fusarium equiseti and Alternaria species using well diffusion and disk diffusion assays. The nanogel exhibited a particle size of 35 ± 4 nm, a PDI of 0.21 ± 0.04, and a zeta potential of −21 ± 3.7 mV, indicating uniform particle distribution and moderate stability. TEM confirmed spherical morphology. The nanogel demonstrated sustained drug release over 32 h, with complete inhibition of fungal growth at a minimum inhibitory concentration (MIC) of 1 %, significantly outperforming conventional Ketoconazole gel. The Ketoconazole-loaded nanogel offers a stable, biocompatible, and highly effective formulation for treating dermatological fungal infections. Its controlled release and superior antifungal activity support its potential for clinical translation, warranting further investigation in patient-centered studies.
Thymoquinone (TQ), the principal bioactive constituent of Nigella sativa, possesses potent antioxidant and anticancer properties but suffers from poor aqueous solubility and limited bioavailability. This study evaluates the therapeutic efficacy of TQ encapsulated within poly(lactic-co-glycolic acid) nanoparticles (TQ-PNPs), synthesized via solvent evaporation and physicochemically characterized by dynamic light scattering, zeta potential measurement, and transmission electron microscopy. 90 female Swiss albino mice were allocated to 6 groups: control, TQ, TQ-PNPs (10 mg/kg, oral), EAC, EAC + TQ, and EAC + TQ-PNPs. Endpoints included tumor viability, hematological and biochemical indices, antioxidant enzyme activity, pro-inflammatory cytokines, oxidative stress biomarkers, and hepatorenal histopathology. Molecular docking assessed TQ binding affinities toward key antioxidant enzymes. Compared to free TQ, TQ-PNPs was associated with significantly greater reductions in tumor burden, inflammatory cytokines (IL-2, IL-6, TNF-α), and oxidative stress markers, with concurrent restoration of antioxidant defenses and enhanced hepatorenal protection. Molecular docking indicated high-affinity interactions between TQ and catalase, superoxide dismutase, and glutathione peroxidase, supporting a plausible mechanistic basis for its antioxidative activity but requiring experimental confirmation. These findings suggest that PLGA-based nanoencapsulation can enhance TQ’s bioavailability and therapeutic index in this murine EAC model, positioning TQ-PNPs as a promising platform for phytochemical delivery in cancer management.
In this piece of work, the phytochemical profile of fruit extract of Artemisia santolinifolia was investigated using HPLC and GC-MS analysis. The extract was then subjected to animal’s rat model for its effect on biochemical and hematological parameters in diabetic animals. The GC-MS and HPLC analysis reflect presence of known chemical compounds. The plant extract lowered the blood glucose level to 191.54 and 177.39 mg/dL at test doses of 125 and 250 mg/kg body weight when compared to diabetic animals having blood glucose level of 416.21 ± 4.20 mg/dL. Similarly, the extracts at doses of 125 and 250 mg/kg lowered the cholesterol level to 97.21 and 110.97 mg/dL correspondingly when compared to diabetic animals (217.25 ± 2.14). The fruit extract reversed the biochemical parameters toward normal range. Diabetes influenced the WBC count in the diabetic group, which was reversed by plant extract. A moderate change in RBC level for the diabetic group was also noted. PCV% and Hb levels were also moderately affected by induced diabetes, which were effectively reversed by plant extract. In light of the current study it may be concluded that the extract is rich in phytochemicals which are biologically active and has the ability to reverse the changes that were caused or produced by diabetes.
Breast cancer is the most prevalent cancer among women, and the leading cause of cancer-related deaths worldwide. Current chemotherapy regimens are not highly effective and often accompanied by severe side effects. Hesperetin (HE) is a bioflavonoid extracted from citrus fruits, which exhibits diverse biological activities including prominent anti-tumor effects. However, its poor water solubility and low stability lead to limited bioavailability upon oral administration and high susceptibility to renal clearance, thereby restricting its clinical application. To improve the bioavailability of HE, we formulated it into nanoparticles and evaluated its in vitro anti-breast cancer efficacy. Specifically, aminoethyl-anisamide amphiphilic polymer polyethylene glycol-poly(ε-caprolactone) (AEAA-PEG-PCL), a carrier with active targeting properties, was employed to encapsulate HE via a nanoprecipitation method, yielding HE nanoparticles (NPs) with small size, uniform particle size distribution, and spherical morphology. These HE NPs achieve sustained release of HE in a simulated tumor microenvironment. Further in vitro cancer cell culture studies were conducted. Compared with unmodified nanoparticles, this targeted delivery system exhibited enhanced tumor cell internalization and significantly inhibited tumor cell proliferation, which indicates its considerable potential in improving breast cancer treatment efficacy. Therefore, HE NPs represent a promising drug delivery platform for breast cancer.
Water sources associated with ancient healing centres were historically believed to possess therapeutic properties, yet their physicochemical, microbiological, and radiological characteristics remain insufficiently documented. In this study, the Sacred Spring and the adjacent Roman-period Immersion Pool at the Pergamene Asklepieion (Bergama, Türkiye) were investigated through a comprehensive integrated assessment. Water samples were collected during two critical hydrological periods (Autumn 2024 and Spring 2025) to evaluate seasonal variability and environmental influences on water quality as part of a pilot initiative for long-term monitoring. Arsenic and selected elemental concentrations were determined using ICP-MS, while microbiological quality was assessed based on ISO standards for Escherichia coli, total coliforms, intestinal enterococci, and total viable counts. To evaluate radiological characteristics, radon (Rn-222) and total alpha activity were measured in the water. Main findings revealed a significant seasonal increase in arsenic concentrations in both water sources, with the Immersion Pool reaching 9.49 ppb in Spring 2025, closely approaching the World Health Organization (WHO) guideline value of 10 ppb. While major ions exhibited similar distributions, microbiological analyses indicated a clear distinction: the Sacred Spring remained free of fecal indicators (E. coli and intestinal enterococci) across both seasons, suggesting a well-protected groundwater source. In contrast, the Immersion Pool showed elevated microbial loads, including detectable E. coli in spring, reflecting higher environmental exposure. Radiological measurements demonstrated that both gross alpha activity (0.010–0.022 Bq/L) and radon concentrations (1.02–5.95 Bq/L) remained consistently below the WHO screening level (0.1 Bq/L) and the EPA regulatory limit (11 Bq/L for radon), indicating no regulatory concern under current conditions. Overall, this research highlights clear differences between the protected Sacred Spring and the environmentally vulnerable Immersion Pool. While the sacred spring maintains a stable profile, the findings establish an essential baseline for the preservation of historical water systems. This study serves as a foundation for future longitudinal research aimed at developing predictive models for the sustainable management of ancient healing waters under changing environmental and climatic conditions. These findings lay groundwork for ongoing monitoring of such heritage waters, stressing the need to safeguard their health and cultural roles amid shifting conditions.
The green synthesis of nanoparticles using plant extracts has attracted increasing attention owing to its eco-friendly nature and enhanced biomedical applications. This study aimed to biosynthesize titanium dioxide nanoparticles using Punica granatum peel extract (TiO2@PGP NPs) and evaluate their physicochemical characteristics, cytotoxic activity against cancer cells, and anticoccidial effects against Eimeria tenella. The nanoparticles were characterized using GC-MS, XRD, TEM coupled with EDS, XPS, FTIR, photoluminescence (PL), and dynamic light scattering (DLS). Cytotoxic activity was assessed using the MTT assay on CaCo-2 cells, while anticoccidial activity was evaluated through in vitro inhibition of oocyst sporulation of E. tenella. FTIR analysis confirmed the presence of functional groups from PGP involved in nanoparticle stabilization. XRD revealed a crystalline size of approximately 7.02 ± 0.8 nm, while TEM showed spherical nanoparticles with an average size of 25.58 ± 4.7 nm. DLS indicated good stability of TiO2@PGP NPs compared to individual components, and PL analysis demonstrated reduced intensity upon PGP incorporation. Biologically, TiO2@PGP NPs exhibited significantly higher cytotoxicity against CaCo-2 cells within 24 h compared to PGP alone and effectively inhibited E. tenella oocyst sporulation within 72 h. The TiO2@PGP NPs demonstrated favorable physicochemical properties, enhanced anticancer cytotoxicity, and strong anticoccidial activity. These findings suggest that TiO2@PGP NPs NPs hold promise for future in vivo cancer therapy applications and as a potential alternative treatment for coccidiosis in poultry.
In this study, graphene oxide/zinc oxide (GO/ZnO) nanocomposite was synthesized for the removal of Nd(III) ions from aqueous solutions. GO was prepared using a modified Tour method, while ZnO nanoparticles were synthesized via the hydrothermal method. The adsorption mechanism highlights through computational modelling, incorporating Quantum Theory of Atoms in Molecules- Non-Covalent Interactions (QTAIM-NCI) and ELF analyses, underscores the potential of GO/ZnO as an effective adsorption system for Nd(III). Detailed DFT calculations, including density of states (DOS), non-covalent interaction analysis, reduced density gradient (RDG) iso-surface, and electron localization function (ELF) analysis have been performed to provide insights into the nature and types of the interactions responsible for the stability of GO/ZnO and the charge transfer processes occurring on the surface of the complex. The nanocomposite was characterized for the morphology, surface chemistry, and functional groups relevant to the Nd(III) adsorption process. Adsorption experiments were conducted at room temperature, optimizing parameters such as pH, initial metal ion concentration, and contact time to maximize Nd(III) removal. The adsorption process was well described by the Langmuir isotherm and followed pseudo-second-order kinetics. The mechanism of the adsorption process was determined from Weber-Morris and Boyd models. The findings suggested that the diffusion rate-limiting process of adsorption was the external mass transport attributed to both the intraparticle and film diffusion. The GO/ZnO nanocomposites exhibited a maximum adsorption capacity of 186.42 ± 3.12 mg/g for Nd(III) ions. Post-adsorption analyses using X-ray photoelectron spectroscopy (XPS) and SEM-EDX confirmed the chemisorption of Nd(III) on the GO/ZnO surface. Thermodynamic demonstrated the spontaneity, endothermic nature, and temperature favor of the adsorption of Nd(III) ions on GO/ZnO. Additionally, density functional theory (DFT) calculations were employed to study the adsorption mechanism, providing insights into the configuration and adsorption energy of Nd(III) on GO/ZnO. These results highlight GO/ZnO nanocomposite as a promising candidate for efficient neodymium ion removal from aqueous environments.
Pseudomonas aeruginosa is a gram-negative pathogen with a high resistance to antibiotics. The World Health Organization declared P. aeruginosa a severe threat to immunocompromised patients. It can survive due to the formation of biofilms. This bacterium’s increasing resistance to antibiotics has necessitated the identification of new therapeutic agents. The geranyl-CoA carboxylase beta subunit (GCC) protein was chosen for in-silico drug development. On the basis of ADMET properties, the “17,967” phytochemicals were screened, and the resultant selection of 97 ligands was made. Out of all, Medicarpin 3-O-glucoside (PubChem ID: 23724664), which had a docking value of −9.9 kcal/mol showed the highest binding affinity. After molecular docking, Density Functional Theory was used to evaluate the electronic properties of the top compounds. Medicarpin 3-O-glucoside showed an energy gap of 0.1936 eV. Molecular dynamics (MD) simulations were conducted for 100 ns to assess the stability of the protein-ligand complex. The results indicated consistent structural stability based on RMSD, RMSF, radius of gyration and hydrogen bonding patterns. These findings suggest that Medicarpin 3-O-glucoside has the potential to act as a stable and effective inhibitor of the GCC protein in P. aeruginosa.
This research aims to design orally fast disintegrating films ODFs for the administration of an anti-migraine drug, sumatriptan succinate (STS). Molecular docking studies were conducted to select the most suitable polymer based on the strength of its interactions with the active substance, that suggest the choice of hydroxypropyl methylcellulose (HPMC). From the preliminary formulation, propylene glycol (PG) was found to be the best plasticizer, while crospovidone (PVPP) was found to be the best super disintegrant. A Box Behnken design was used for the optimization of the formulations, including the effects of the concentrations of the polymer, the plasticizer, and the crospovidone. This design also included the responses of the formulations, such as the disintegration time, the folding endurance, and the drug release after 3 min. The ODFs were analyzed using FTIR-ATR, DSC, and SEM. Their disintegration time as well as their active ingredient release profile were evaluated. Other parameters were considered such as: active ingredient content, thickness, pH and folding endurance. Statistical analysis confirmed that formulation variables significantly impacted the selected responses. The optimized formulation (F opt) had a disintegration time of 35 s and 90 % of STS released within 3 min, the release data showed best fit to Korsmeyer–Peppas model with R 2 of 0.974.
Dengue fever remains a major global health concern due to the absence of approved antiviral therapies specifically targeting dengue virus infection. In this study, an integrated in silico drug repurposing strategy was employed to identify potential therapeutic candidates against dengue virus. The first approach combined electron–ion interaction potential (EIIP)-guided screening of FDA-approved compounds with molecular docking against the dengue virus prM–E envelope glycoprotein complex, followed by post-docking MM-GBSA rescoring of selected candidates to refine binding affinity predictions. The second approach applied network-based drug repurposing using the Drugst.One platform, incorporating disease-associated human gene networks to identify compounds with potential host-directed therapeutic relevance. The EIIP–docking workflow identified several promising candidates, particularly antiviral agents such as acyclovir, ganciclovir, and entecavir, as well as compounds including dantrolene and ephedrine. MM-GBSA analysis supported the stability of acyclovir and ganciclovir binding, while highlighting limitations of docking-only ranking for certain candidates. Network-based analysis independently identified clinically relevant compounds, including atorvastatin, rosuvastatin, ciclesonide, mycophenolic acid, and dantrolene, suggesting overlap between viral-targeted and host-centered repurposing strategies. ADMET profiling further prioritized compounds with favorable pharmacokinetic and toxicity characteristics. These findings demonstrate that integrating structure-based and network-based computational repurposing approaches can efficiently identify promising dengue therapeutic candidates for future experimental validation.
Abstract This study investigated the glass system 45B 2 O 3 –30BaO-25sZnO, with ‘s’ indicating the micro, nano, and micro+nano ZnO particle size. The gamma-ray shielding performance test was performed after the glass preparation process, with the test being conducted experimentally using the narrow beam method. Various gamma sources and an HPGe detector were used. The linear attenuation coefficient (LAC) of the glass system was calculated using Phy-x software, and good agreement was obtained between the experimental LAC and the Phy-X LAC in the results, such as 0.298 cm −1 measured at 0.662 MeV, which is close to the Phy-X data of 0.305 cm −1 . Glass reinforced with a mixture of nano- and micro-sized zinc oxide particles recorded higher attenuation coefficient values compared to systems containing only one size of ZnO particles, indicating that the combination of nano and micro gives better radiation attenuation performance. At 1.333 MeV, the half-value layer was 3.37, 3.29 and 3.17 cm for micro-ZnO, nano-ZnO and (micro+nano)-ZnO, respectively. This study contributes to expanding the understanding of the effect of particle size on attenuation properties, and opens the door to further research towards the design of advanced systems with improved performance in radiation shielding applications.
Porous starches are a kind of promising inclusion materials for controlled flavor release. However, few researches on the preparation of porous starch inclusion materials with maple syrup extract have been reported. In this study, porous starches were yielded by alcohol-hydrothermal pre-treatment in combination with enzymatic hydrolysis, which was optimized using single factor experiments. The porous starches including maple syrup extract were prepared into granule, and the morphology characteristics and controlled release effects were determined. It was found that alpha-amylase to glucoamylase ratio of 1:1, addition amount of 1.5 g, and time of 12 h were the optimized enzymatic hydrolysis conditions. Scanning electron microscopy (SEM) suggested the starches became porous after enzymatic hydrolysis, which absorbed maple syrup extract successfully as confirmed by fourier transform infrared spectroscopy (FT-IR). After being made into granules, the controlled release ability significantly increased, and the flavor compound residual amount in granules (63.16 %) was obviously higher than that of the maple syrup extract (19.27 %) at 30 days of storage. The typical flavor compounds of maple granules were determined as phenylethyl alcohol, beta-ionone, and 4-hydroxy-2,5-dimethyl-3(2H)furanone, which could bring flora and sweet aromas. The suitable release temperature was suggested as 60 degrees C, and the flavor-enhancing effects were also determined.
The radiation shielding parameters of lead borosilicate glasses were examined to assess their potential in different radiation shielding applications. The shielding parameters of the investigated glasses were estimated within the 0.0359–1.46 MeV interval. The transmission factor values increase as the incoming energy increases, suggesting that more photons transmit through the glasses when they have higher energies. The TF results also showed that adding more PbO 2 and removing B 2 O 3 in the glasses leads to a smaller TF, and therefore a more effective shield. The radiation protection efficiency (RPE) was calculated and the results demonstrated that glass with higher PbO 2 content has a greater shielding ability at all tested energies. At very low energies, the RPE of the glasses is essentially equal to 1, meaning that all of the incoming photons are absorbed by the glasses. The linear attenuation coefficient was investigated and the maximum LAC was reported at 0.0395 MeV, ranging from 43.711 to 58.409 cm −1 .
Malaria, primarily caused by Plasmodium parasites, remains a major public health challenge, especially in regions with emerging drug resistance. Among the Plasmodium species, Plasmodium berghei (Pb) induces severe infections in experimental models. This study investigated the anti-apoptotic effects of walnut (Juglans regia L.) leaf extract (JRLE) in C57BL/6 mice infected with Pb. Methanolic extracts of JRLE were characterized using LC-ESI-MS, revealing alkaloids, phenolics, flavonoids, anthocyanins, fatty acids, and sterols. Six groups of female mice (n = 5 each) were established, including controls, non-infected JRLE-treated, and Pb-infected groups treated with JRLE (250 or 500 mg/kg) or chloroquine (10 mg/kg). Pb infection was induced intraperitoneally, and treatments were administered orally from day 4 to 8. Blood and brain samples were collected on day 9 for hematological and immunohistochemical analyses, and parasitemia, suppression rates, and feed intake were assessed. JRLE significantly reduced parasitemia (43.87 % at 250 mg/kg; 72.84 % at 500 mg/kg), improved feed intake, restored hemoglobin and erythrocyte levels, and normalized white blood cell counts. Additionally, JRLE lowered elevated caspase-3 expression in infected mice, indicating a protective effect against apoptosis. These findings suggest that walnut leaf extract, rich in bioactive phytochemicals, may offer anti-plasmodial activity and reduced brain caspase-3 signal in malaria infection.
Cytisus villosus and Cistus laurifolius, traditionally used in Mediterranean herbal medicine for metabolic disorders, remain insufficiently characterized for their antidiabetic activity. This study investigated polyphenol-rich aqueous extracts using integrated in vitro, in vivo, and in silico approaches. HPLC analysis, based on comparison with authentic standards, identified gallic acid, hydroxybenzoic acid, caffeic acid, p-coumaric acid, rutin, quercetin, and catechin in both extracts; syringic acid was detected only in C. villosus, whereas salicylic acid was specific to C. laurifolius. In pancreatic alpha-amylase inhibition assays, IC50 values were 125.73 +/- 3.23 mu g/mL and 113.10 +/- 2.14 mu g/mL, respectively. In alloxan-induced diabetic rats (n = 6 per group), daily oral administration of 500 mg/kg for 28 days significantly reduced fasting blood glucose from day 7 onward (P < 0.05), with final decreases of 47.07 % and 50.95 %, compared to 41.75 % in the glibenclamide group. Improvements in lipid profile and reductions in ASAT, ALAT, creatinine, and urea were observed. No acute toxicity was detected at 2000 mg/kg. Molecular docking supported alpha-amylase inhibition as a contributing mechanism. These findings indicate significant antidiabetic potential of both extracts and support further pharmacological investigation.
Pesticide residues are toxic contaminants in agricultural products, threatening human health throughout the food chain. In this paper, an electrochemiluminescence (ECL) sensor based on rough Ru(bpy)(3)(2+)-doped silica nanoparticles (rSiO(2)@Ru(bpy)(3)(2+) NPs) was developed for the sensitive detection of permethrin (PET) residues in vegetables. The sensor was fabricated by modifying a glassy carbon electrode (GCE) with graphene hydrogel (GH). The ECL produced by the rSiO(2)@Ru(bpy)(3)(2+)/tripropylamine (TPA) system exhibited a proportional quenching response to the concentration of PET, leading to a decrease in the ECL intensity. Under optimized conditions, the ECL intensity showed a linear relationship with the logarithm of PET concentration across a wide range from 1.0 & times; 10(-11) M to 1.0 & times; 10(-7) M, with a detection limit of 3.3 & times; 10(-12) M (S/N = 3). The proposed sensor demonstrated high sensitivity and was successfully applied to determine PET levels in real vegetable samples, offering a reliable approach for monitoring pesticide residues in agricultural products.
Monotropa uniflora is a saprophytic plant with unexplored medicinal potential. In this study, the salicylic acid (SA)-induction was applied to M. uniflora for the first time. Coupled with a systematic research framework integrating data-driven analysis, computational prediction, and experimental validation, we investigated the active components of M. uniflora and their molecular mechanisms against colorectal cancer (CRC). Untargeted metabolomics identified 1,644 metabolites, with 458 being differentially expressed after SA induction. Notably, levels of secondary metabolites such as dalbergin (DL) and sanguinarine (SAN) were significantly up-regulated. Network pharmacology identified polyporusterone G, betavulgarin, DL, SAN, and deoxynivalenol as core candidates targeting key proteins like STAT3 and EGFR. Molecular docking confirmed strong binding (binding energy <= -5 kcal/mol), with SAN exhibiting particularly high affinity for MAPK3 (Delta G = -10.7 kcal/mol). In vitro validation showed that both DL and SAN potently inhibited the viability of HCT116 and SW480 cells. DL exhibited IC50 values as low as 2.268 mu M (SW480, 48 h), while SAN showed an IC50 of 3.479 mu M (SW480, 48 h). This study is the first to apply SA-induction to M. uniflora, systematically identifying DL and SAN as key anti-CRC constituents through an integrated approach, thereby providing a foundation for its development as a source of anti-CRC agents.
