Malva sylvestris leaf powder as a feed additive affects the performance, carcass traits, meat quality attributes, serum antioxidants, stress physiology, intestinal bacterial counts, and gut morphology of broiler chicken.

This study investigated the effect of supplementation of Malva sylvestris leaf powder (MSLP) on the production performance of broiler chicken. Ven Cobb broiler chicks (240 day-old male chicks) were distributed randomly into four treatments, each replicated four times, with 15 birds per replicate. The diets formulated were T1 (control) given basal diet only, T2 (basal diet +1.0% MSLP), T3 (basal diet +1.5% MSLP), and T4 (basal diet +2.0% MSLP). The highest improvement of 3.83% in the average daily gain (ADG) was recorded in the T3 group fed 1.5% Malva powder in the diet compared to the control (P = 0.009). The average daily feed intake (ADFI) tended to decrease with an increase in the dose of MSLP in the diet, with the lowest feed intake in the T4 group fed 2% MSLP. During the overall period (7-42 days), the feed/gain (F/G) ratio reduced significantly (P = 0.048) in the T3 and T4 groups compared to the control. The dressed and breast meat yield was found to be significantly (P < 0.05) higher in the T3 group, with no significant change (P > 0.05) in the thigh yield. The changes in the pH and water-holding capacity (WHC) of breast meat were found to be non-significant (p > 0.05) between the control and various other treatments. Thiobarbituric acid-reactive substances (TBARS) were significantly (P < 0.05) decreased in the T3 and T4 groups. There was no negative effect of including MSLP in the diet on the color coordinates of breast meat among different treatments. Compared to the control, the serum immunoglobulin values increased significantly (P < 0.05) in the T3 and T4 groups. Superoxide dismutase (SOD) showed no difference between various treatments; however, malondialdehyde (MDA) decreased significantly (P < 0.05) according to dietary treatments. Serum cortisol increased significantly (P < 0.05) in the T4 group compared to other treatments. The inclusion of Malva powder in the diet at the 2% level significantly (P < 0.05) decreased the coliform count compared to the control birds. Supplementation with Malva powder resulted in a significant (P < 0.05) increase in the villus height-to-crypt depth (VH:CD) ratio of broiler birds in the T3 and T4 groups. In conclusion, MSLP supplementation at 1.5% and 2% resulted in improved production performance of broiler chicken.

Enhanced remediation of U(vi) ions from water resources using advanced forms of morphologically modified glauconite (nano-sheets and nano-rods): experimental and theoretical investigations.

Two forms of morphologically transformed glauconite (GL) involved exfoliated nanosheets (EXG) and nanorods (GRs), which were synthesized by facile exfoliating and scrolling modification under sonication. The two advanced forms (EXG and GRs) were applied as enhanced adsorbents for U(vi) ions and compared with using raw glauconite. The developed GRs structure displays higher saturation retention properties (319.5 mg g-1) in comparison with both EXG (264.8 mg g-1) and GL (237.9 mg g-1). This enhancement is assigned to the noticeable increment in the surface area (32.6 m2 g-1 (GL), 86.4 m2 g-1 (EXG), and 123.7 m2 g-1 (GRs)) in addition to the surface reactivity and exposure of effective siloxane groups. This was supported by the steric investigation based on the isotherm basics of the monolayer model of one energy site. The steric functions declared a strong increase in the density of the existing effective uptake receptors throughout the modification stages (GRs (112.1 mg g-1) > EXG (87.7 mg g-1) > 72.5 mg g-1 (GL)). Also, each active site can be filled with 4 U(vi) ions, donating the parallel orientation of these ions and the operation of multi-ionic mechanisms. The energetic functions, either the uptake energy (<13 kJ mol-1) or Gaussian energy (<5 kJ mol-1), validate the retention of U(vi) by physical reactions. These reactions displayed spontaneous properties and exothermic behaviors based on the investigated thermodynamic functions, including entropy, enthalpy, and internal energy. The structures also showed significant recyclability, indicating potential application on a realistic and commercial scale.

Insight into the integration effect of chitosan and ß-cyclodextrin on the properties of zinc-phosphate/hydroxyapatite hybrid as delivery structures for 5-fluorouracil: loading and release profiles.

Zinc-phosphate/hydroxyapatite hybrid form (ZP/HP) in core-shell nanostructure was developed and functionalized with both chitosan (CS@ZP/HP) and ß-cyclodextrin (CD@ZP/HP) as bio-composite of enhanced physicochemical and biological properties. These structures were assessed as potential deliveries of 5-fluorouracil, exhibiting enhanced loading, release, and anti-cancer behaviors. The functionalization strongly prompted the loading effectiveness to be 301.3 mg/g (CS@ZP/HP) and 342.8 mg/g (CD@ZP/HP) instead of 238.9 mg/g for ZP/HP. The loading activities were assessed based on the hypotheses of traditional kinetic and isotherm models, alongside the computational variables of the monolayer model with a single energetic site as an advanced isotherm model. The functionalized versions exhibit much greater loading efficacy compared to ZP/HP as a result of the increment in the density of the existing loading sites [Nm(5-Fu) = 78.85 mg/g (ZP/HP), 93.87 mg/g (CS@ZP/HP), and 117.8 mg/g (CD@ZP/HP)]. Furthermore, the loading energies of approximately 40 kJ/mol, together with the loading potential of each receptor (n > 1) and Gaussian energies of approximately 8 kJ/mol, indicate the physical entrapment of 5-Fu molecules according to a vertical orientation. The materials mentioned verify long-term and continuous release characteristics. Following the modification processes, this behavior became faster as both CS@ZP/HP and CD@ZP/HP displayed complete release within 120 h at pH 1.2. The kinetic studies and diffusing exponent (>0.45) indicate that release characteristics are controlled by both diffusion and erosion processes. These carriers also markedly increase the cytotoxicity of 5-Fu against HCT-116 colorectal cancer cell lines: 5-Fu-ZP/HP (3.2% cell viability), 5-Fu-CS@ZP/HP (1.12% cell viability), and 5-Fu-CD@ZP/HP (0.63% cell viability).

Effects of α-sitosterol on growth, hematobiochemical profiles, immune-antioxidant resilience, histopathological features and expression of immune apoptotic genes of Nile tilapia, Oreochromis niloticus, challenged with Candida albicans.

In this study, the effect of the Streptomyces misakiensis metabolite (α- sitosterol, 0, 20, 40, 60, and 80 mg/kg) dietary supplementation on growth performance, antioxidant-immune stability and Candida albicans resistance of Nile tilapia was evaluated. The results revealed that the incorporation of α-sitosterol at doses of 60 and 80 mg/kg into the diet significantly improved the growth rate of Nile tilapia. The fish receiving 80 mg/kg showed an increased level of high-density lipoprotein, total protein, globulin, and albumin, and significantly reduced levels of indicators of hepato-renal damage, glucose, triglycerides, low-density lipoprotein, and total cholesterol. Dietary α-sitosterol induced a considerable increase in hepatopancreas glutathione peroxidase, superoxide dismutase and catalase activities and a significant drop in malondialdehyde levels. Supplementing the diet with 80 mg/kg of α-sitosterol increased nitric oxide, complement-3, nitro blue tetrazolium levels, lysozyme, and phagocytic activities. In particular, supplementing with α-sitosterol at 60-80 mg/kg of diet significantly enhanced the expression of pro/anti-inflammatory markers (il1b, il10, tgfb, ifng, tnfa and il8) after the C. albicans challenge. Also, there was a decrease in cumulative mortality percent, pro-apoptotic markers (casp3, bax and hsp70) and an increase in anti-apoptotic indicators (bcl2). Interestingly, following the C. albicans challenge, fish that received 0 and 20 mg α-sitosterol/kg exhibited significant inflammation in the hepatopancreas, spleen, and intestine. On the other hand, inflammation could be alleviated by feeding 60-80 mg α-sitosterol/kg. Due to these findings, α-sitosterol could be an innovative option to enhance growth, general physiological status, immune service, and antifungal resistance of Nile tilapia against C. albicans.

Relationship among micro-pollutants, economic growth, renewable energy, nanotechnology and ecological foot prints of China: evidence from panel data analysis.

An important concern is the availability of clean drinking water, which is an essential need for human survival. This issue arises due to the existence of hazardous micropollutants originating from various emission sources. Nanotechnology aids in the mitigation of micropollutants by assimilating and counteracting their effects, hence diminishing their influence on water and other ecosystems. The study investigates the relationship between nanotechnological progress, the adoption of renewable energy, environmental consequences, and economic growth in China, using the Environmental Kuznets Curve theory as a conceptual framework. The study employs panel cointegration tests to analyze structural breaks from 2000 to 2020. Nanotechnology is expected to reduce environmental degradation and the presence of micro-pollutants by increasing the use of renewable energy and promoting energy conservation. Nanotechnology is crucial for mitigating micro-pollutants and advancing sustainable development in this specific context. However, the literature also highlights the harmful consequences of nanoparticle emissions caused by nanotechnology on human and environmental health for a long duration, requiring more examination. This research is the first empirical inquiry into the relationship between improvements in nanotechnology, the use of renewable energy, economic growth, and ecological effect, all within the context of the Environmental Kuznets Curve theory. The results confirm the successful incorporation of all components with a focus on long-term outcomes. The findings suggest that the EKC hypothesis is relevant in China. In China, advancements in nanotechnology have a moderating effect on environmental degradation. The use of renewable energy sources in China enhances environmental circumstances. Given the offered empirical evidence, it is advisable for the government to have a leading role in the development of innovative nanotechnologies that have low emissions of nanoparticles. By using this approach, it will be possible to encourage the conservation of energy and the use of renewable sources in a more secure way, hence improving the effectiveness of sustainable development initiatives.

Synthesis and characterization of cellulose fibers modified zinc phosphate/hydroxyapatite core-shell as enhanced carrier of cisplatin: Loading, release, and cytotoxicity.

The uncontrolled administration of the cisplatin drug (CPTN) resulted in numerous drawbacks. Therefore, effective, affordable, and biocompatible delivery systems were suggested to regulate the loading, release, and therapeutic effect of CPTN. Zinc phosphate/hydroxyapatite hybrid form (ZP/HP) and core-shell nano-rod morphology, as well as its functionalized derivative with cellulose (CF@ZP/HP), were synthesized by the facile dissolution precipitation method followed by mixing with cellulose fibers, respectively. The developed CF@ZP/HP displayed remarkable enhanced CPTN loading properties (418.2 mg/g) as compared to ZP/HP (259.8 mg/g). The CPTN loading behaviors into CF@ZP/HP follow the Langmuir isotherm properties (R2 > 0.98) in addition to the kinetic activities of the pseudo-first-order model (R2 > 0.96). The steric assessment validates the notable increase in the existing loading receptors after the functionalization of ZP/HP with CF from 57.7 mg/g (ZP/HP) to 90.5 mg/g. The functionalization also impacted the capacity of each existing receptor to be able to ensure 5 CPTN molecules. This, in addition to the loading energies (<40 kJ/mol), donates the loading of CPTN by physical multi-molecular processes and in vertical orientation. The CPTN releasing patterns of CF@ZP/HP exhibit slow and controlled properties (95.7 % after 200 h at pH 7.4 and 100 % after 120 h at pH 5.5), but faster than the properties of ZP/HP. The kinetic modeling of the release activities together with the diffusion exponent (>0.45) reflected the release of CPTN according to both erosion and diffusion mechanisms. The loading of CPTN into both ZP/HP and CF@ZP/HP also resulted in a marked enhancement in the anticancer activity of CPTN against human cervical epithelial malignancies (HeLa) (cell viability = 5.6 % (CPTN), 3.2 % (CPTN loaded ZP/HP), and 1.12 % (CPTN loaded CF@ZP/HP)).

Dissecting molecular mechanisms underlying the inhibition of ß-glucuronidase by alkaloids from Hibiscus trionum: Integrating in vitro and in silico perspectives.

ß-Glucuronidase, a crucial enzyme in drug metabolism and detoxification, represents a promising target for therapeutic intervention due to its potential to modulate drug pharmacokinetics and enhance therapeutic efficacy. Herein, we assessed the inhibitory potential of phytochemicals from Hibiscus trionum against ß-glucuronidase. Grossamide and grossamide K emerged as the most potent ß-glucuronidase inhibitors with IC50 values of 0.73 ± 0.03 and 1.24 ± 0.03 µM, respectively. The investigated alkaloids effectively inhibited ß-glucuronidase-catalyzed PNPG hydrolysis through a noncompetitive inhibition mode, whereas steppogenin displayed a mixed inhibition mechanism. Molecular docking analyses highlighted grossamide and grossamide K as inhibitors with the lowest binding free energy, all compounds successfully docked into the same main binding site occupied by the reference drug Epigallocatechin gallate (EGCG). We explored the interaction dynamics of isolated compounds with ß-glucuronidase through a 200 ns molecular dynamics (MD) simulation. Analysis of various MD parameters revealed that grossamide and grossamide K maintained stable trajectories and demonstrated significant energy stabilization upon binding to ß-glucuronidase. Additionally, these compounds exhibited the lowest average interaction energies with the target enzyme. The MM/PBSA calculations further supported these findings, showing the lowest binding free energies for grossamide and grossamide K. These computational results are consistent with experimental data, suggesting that grossamide and grossamide K could be potent inhibitors of ß-glucuronidase.

Deciphering molecular mechanisms underlying the inhibition of ß-glucuronidase by xanthones from Centaurium spicatum.

Herein, we scrutinized the inhibitory potential of five xanthones and a flavonoid, sourced from Centaurium spicatum, against ß-glucuronidase activity. The results showed that gentisin and azaleatin emerged as the most potent inhibitors, with significantly lower IC50 values of 0.96 ± 0.10 and 0.57 ± 0.04 µM, respectively. The evaluation of enzyme kinetics unveiled that the isolated xanthones manifested inhibition of ß-glucuronidase through a mixed inhibition mode, whereas azaleatin exhibited a noncompetitive inhibition mechanism. The findings from molecular docking analysis unveiled that the compounds under investigation, particularly azaleatin, displayed comparatively diminished binding affinities towards ß-glucuronidase. Furthermore, the tested drugs were shown to occupy a common binding site as the employed reference drug. Our comprehensive Molecular Dynamics (MD) simulations analysis revealed consistent trajectories for the investigated drugs, wherein azaleatin and gentisin demonstrated notable stabilization of energy levels. Analysis of various MD parameters revealed that drugs with the lowest IC50 values maintained relatively stable interactions with ß-glucuronidase. These drugs were shown to exert notable alterations in their conformation or flexibility upon complexation with the target enzyme. Conversely, the flexibility and accessibility of ß-glucuronidase was reduced upon drug binding, particularly with azaleatin and gentisin, underscoring the stability of the drug-enzyme complexes. Analysis of Coul-SR and LJ-SR interaction energies unveiled consistent and stable interactions between certain isolated drugs and ß-glucuronidase. Azaleatin notably displayed the lowest average Coul-SR interaction energy, suggesting strong electrostatic interactions with the enzyme's active site and significant conformational variability during simulation. Remarkably, LJ-SR interaction energies across different xanthones complexes were more negative than their Coul-SR counterparts, emphasizing the predominant role of van der Waals interactions, encompassing attractive dispersion and repulsive forces, in stabilizing the drug-enzyme complexes rather than electrostatic interactions.

Bridging in silico and in vitro perspectives to unravel molecular mechanisms underlying the inhibition of ß-glucuronidase by coumarins from Hibiscus trionum.

Unraveling the intricacies of ß-glucuronidase inhibition is pivotal for developing effective strategies in applications specific to gastrointestinal health and drug metabolism. Our study investigated the efficacy of some Hibiscus trionum phytochemicals as ß-glucuronidase inhibitors. The results showed that cleomiscosin A and mansonone H emerged as the most potent inhibitors, with IC50 values of 3.97 ± 0.35 µM and 10.32 ± 1.85 µM, respectively. Mechanistic analysis of ß-glucuronidase inhibition indicated that cleomiscosin A and the reference drug EGCG displayed a mixed inhibition mode against ß-glucuronidase, while mansonone H exhibited noncompetitive inhibition against ß-glucuronidase. Docking studies revealed that cleomiscosin A and mansonone H exhibited the lowest binding affinities, occupying the same site as EGCG, and engaged significant key residues in their binding mechanisms. Using a 30 ns molecular dynamics (MD) simulation, we explored the interaction dynamics of isolated compounds with ß-glucuronidase. Analysis of various MD parameters showed that cleomiscosin A and mansonone H exhibited consistent trajectories and significant energy stabilization with ß-glucuronidase. These computational insights complemented experimental findings, underscoring the potential of cleomiscosin A and mansonone H as ß-glucuronidase inhibitors.

Correction: Characterization of chitosan- and ß-cyclodextrin-modified forms of magnesium-doped hydroxyapatites as enhanced carriers for levofloxacin: loading, release, and anti-inflammatory properties.

[This corrects the article DOI: 10.1039/D4RA02144D.].

Characterization of chitosan- and ß-cyclodextrin-modified forms of magnesium-doped hydroxyapatites as enhanced carriers for levofloxacin: loading, release, and anti-inflammatory properties.

An advanced form of magnesium-rich hydroxyapatite (Mg·HAP) was modified with two types of biopolymers, namely chitosan (CH/Mg·HAP) and ß-cyclodextrin (CD/Mg·HAP), producing two types of bio-composites. The synthesized materials were developed as enhanced carriers for levofloxacin to control its loading, release, and anti-inflammatory properties. The polymeric modification significantly improved the loading efficiency to 281.4 mg g-1 for CH/Mg·HAP and 332.4 mg g-1 for CD/Mg·HAP compared with 218.3 mg g-1 for Mg·HAP. The loading behaviors were determined using conventional kinetic and isotherm models and mathematical parameters of new equilibrium models (the monolayer model of one energy). The estimated density of effective loading sites (Nm (LVX) = 88.03 mg g-1 (Mg·HAP), 115.8 mg g-1 (CH/Mg·HAP), and 138.5 mg g-1 (CD/Mg·HAP)) illustrates the markedly higher loading performance of the modified forms of Mg·HAP. Moreover, the loading energies (<40 kJ mol-1) in conjunction with the capacity of each loading site (n > 1) and Gaussian energies (<8 kJ mol-1) signify the physical trapping of LVX molecules in vertical orientation. The addressed materials validate prolonged and continuous release behaviors. These behaviors accelerated after the modification procedures, as the complete release was identified after 160 h (CH/Mg·HAP) and 200 h (CD/Mg·HAP). The releasing behaviors are regulated by both diffusion and erosion mechanisms, according to the kinetic investigations and diffusion exponent analysis (>0.45). The entrapping of LVX into Mg·HAP induces its anti-inflammatory properties against the generation of cytokines (IL-6 and IL-8) in human bronchial epithelia cells (NL20), and this effect displays further enhancement after the integration of chitosan and ß-cyclodextrin.

Antioxidant and Anti-inflammatory Applications of Aerva persica Aqueous-Root Extract-Mediated Synthesis of ZnO Nanoparticles.

In the present study, ZnO nanoparticles were synthesized by using aqueous extracts of Aerva persica roots. Characterization of as-prepared ZnO nanoparticles was carried out using different techniques, including powder X-ray diffraction (XRD), UV-vis diffuse reflectance spectroscopy (DRS), Fourier transform infrared (FTIR) spectroscopy, field emission scanning electron microscopy (FESEM), transmission electron microscopy (TEM) and BET surface area analysis. Morphological analysis confirmed the small, aggregated flake-shaped morphology of as-synthesized ZnO nanostructures. The as-prepared ZnO nanoparticles were analyzed for their potential application as anti-inflammatory (using in vivo inhibition of carrageenan induced paw edema) and antioxidant (using in vitro radical scavenging activity) agents. The ZnO nanoparticles were found to have a potent antioxidant and anti-inflammatory activity comparable to that of standard ascorbic acid (antioxidant) and indomethacin (anti-inflammatory drug). Therefore, due to their ecofriendly synthesis, nontoxicity, and biocompatible nature, zinc oxide nanoparticles synthesized successfully from roots extract of the plant Aerva persica with potent efficiencies can be utilized for different biomedical applications.

Hibiscetin attenuates lipopolysaccharide-evoked memory impairment by inhibiting BDNF/caspase-3/NF-κB pathway in rodents.

This study explores the neuroprotective potential of hibiscetin concerning memory deficits induced by lipopolysaccharide (LPS) injection in rats. The aim of this study is to evaluate the effect of hibiscetin against LPS-injected memory deficits in rats. The behavioral paradigms were conducted to access LPS-induced memory deficits. Various biochemical parameters such as acetyl-cholinesterase activity, choline-acetyltransferase, antioxidant (superoxide dismutase, glutathione transferase, catalase), oxidative stress (malonaldehyde), and nitric oxide levels were examined. Furthermore, neuroinflammatory parameters such as tumor necrosis factor-α, interleukin-1ß (IL-1ß), IL-6, and nuclear factor-kappa B expression and brain-derived neurotrophic factor as well as apoptosis marker i.e., caspase-3 were evaluated. The results demonstrated that the hibiscetin-treated group exhibited significant recovery in LPS-induced memory deficits in rats by using behavioral paradigms, biochemical parameters, antioxidant levels, oxidative stress, neuroinflammatory markers, and apoptosis markers. Recent research suggested that hibiscetin may serve as a promising neuroprotective agent in experimental animals and could offer an alternative in LPS-injected memory deficits in rodent models.

Are anticoagulant drugs ecotoxic for meiobenthic nematodes from Saudi Arabia? First data on taxon/functional diversity and computational evidences.

Community-level effects of anticoagulants have little been studied in the laboratory. In the current study, the different effects of Warfarin and Tinzaparin, individually or in combination, on meiofauna were investigated for the first time using two concentrations (5 and 25 mg·l-1) of Warfarin (W1 and W2) and Tinzaparin (T1 and T2) for 30 days. The results obtained highlighted the highest tolerance of nematodes and amphipods toward the two anticoagulants tested. Moreover, nematode abundance and taxonomic diversity decreased directly after exposure to T2 and T2W1 because of the high mortality of diatom feeders and their replacement by non-selective deposit feeders (case of Tinzaparin) or omnivores-carnivores (case of Warfarin). The relative taxon/functional similarity between controls and mixtures T1W1 and T2W2 recommends that the toxicity of Tinzaparin can be attenuated by Warfarin. Finally, the computational study of Warfarin supports its potential ecotoxicity since it satisfactorily bound and interacted with GLD-3 and SDP macromolecules.

Cadmium-induced lung injury is associated with oxidative stress, apoptosis, and altered SIRT1 and Nrf2/HO-1 signaling; protective role of the melatonin agonist agomelatine.

Cadmium (Cd) is a hazardous heavy metal extensively employed in manufacturing polyvinyl chloride, batteries, and other industries. Acute lung injury has been directly connected to Cd exposure. Agomelatine (AGM), a melatonin analog, is a drug licensed for treating severe depression. This study evaluated the effect of AGM against Cd-induced lung injury in rats. AGM was administered in a dose of 25 mg/kg/day orally, while cadmium chloride (CdCl2) was injected intraperitoneally in a dose of 1.2 mg/kg to induce lung injury. Pre-treatment with AGM remarkably ameliorated Cd-induced lung histopathological abrasions. AGM decreased reactive oxygen species (ROS) production, lipid peroxidation, suppressed NDAPH oxidase, and boosted the antioxidants. AGM increased Nrf2, GCLC, HO-1, and TNXRD1 mRNA, as well as HO-1 activity and downregulated Keap1. AGM downregulated Bax and caspase-3 and upregulated Bcl-2, SIRT1, and FOXO3 expression levels in the lung. In conclusion, AGM has a protective effect against Cd-induced lung injury via its antioxidant and anti-apoptotic effects mediated via regulating Nrf2/HO-1 and SIRT1/FOXO3 signaling.

Development of Statistically Optimized Piperine-Loaded Polymeric Nanoparticles for Breast Cancer: In Vitro Evaluation and Cell Culture Studies.

Piperine (PPN) is a natural alkaloid derived from black pepper (Piper nigrum L.) and has garnered substantial attention for its potential in breast cancer therapy due to its diverse pharmacological properties. However, its highly lipophilic characteristics and poor dissolution in biological fluids limit its clinical application. Therefore, to overcome this limitation, we formulate and evaluate PPN-encapsulated polycaprolactone (PCL) nanoparticles (PPN-PCL-NPs). The nanoparticles were prepared by a single-step nanoprecipitation method and further optimized by a formulation design approach. The influence of selected independent variables PCL (X1), poloxamer 188 (P-188; X2), and stirring speed (SS; X3) were investigated on the particle size (PS), polydispersity index (PDI), and % encapsulation efficiency (EE). The selected optimized nanoparticles were further assessed for stability, in vitro release, and in vitro antibreast cancer activity in the MCF-7 cancer cell line. The PS, PDI, zeta potential, and % EE of the optimized PPN-PCL-NPs were observed to be 107.61 ± 5.28 nm, 0.136 ± 0.011, -20.42 ± 1.82 mV, and 79.53 ± 5.22%, respectively. The developed PPN-PCL-NPs were stable under different temperature conditions with insignificant changes in their pharmaceutical attributes. The optimized PPN-PCL-NPs showed a burst release for the first 6 h and later showed sustained release for 48 h. The PPN-PCL-NPs exhibit exceptional cytotoxic effects in MCF-7 breast tumor cells in comparison with the native PPN. Thus, the formulation of PPN-loaded PCL-NPs can be a promising approach for better therapeutic efficacy against breast cancer.

Characterization of Chitosan-Hybridized Diatomite as Potential Delivery Systems of Oxaliplatin and 5-Fluorouracil Drugs: Equilibrium and Release Kinetics.

The current work involves the modification of diatomite's biosiliceous frustules employing chitosan polymer chains (CS/Di) to serve as low-cost, biocompatible, multifunctional, and enhanced pharmaceutical delivery systems for 5-fluorouracil (5-Fu) together with oxaliplatin (OXPL). The CS/Di carrier displayed strong loading characteristics, notably at saturation (249.17 mg/g (OXPL) and 267.6 mg/g (5-Fu)), demonstrating a substantial 5-Fu affinity. The loading of the two types of medications onto CS/Di was conducted based on the kinetic behaviors of the conventional pseudo-first-order theory (R2 > 0.90). However, while the loading of OXPL follows the isotherm assumptions of the classic Langmuir model (R2 = 0.99), the loading of 5-Fu displays Fruendlich isotherm properties. Therefore, the 5-Fu loading displayed physical, heterogeneous, and multilayer loading properties, whereas the loading of OXPL occurred in homogeneous and monolayer form. The densities of occupied active sites of CS/Di were 37.19 and 32.8 mg/g for the sequestrations of OXPL and 5-Fu, respectively. Furthermore, by means of multimolecular processes, each loading site of CS/Di can bind up to 8 molecules of OXPL and 9 molecules of 5-Fu in a vertical orientation. This observation explains the higher loading capacities of 5-Fu in comparison to OXPL. The loading energies, which exhibit values <40 kJ/mol, provide confirmation of the dominant and significant consequences of physical processes as the regulating mechanisms. The release patterns of OXPL and 5-Fu demonstrate prolonged features over a duration of up to 120 h. The release kinetic simulation and diffusion exponents which are more than 0.45 provide evidence of the release of OXP and 5-Fu via non-Fickian transportation characteristics and the erosion/diffusion mechanism. The CS/Di carrier exhibited a substantial enhancement in the cytotoxicity of OXPL and 5-Fu against HCT-116 carcinoma cell lines, resulting in a reduction in cell viability by 4.61 and 2.26% respectively.

Synthesis, Characterization, and Biological Properties of Iron Oxide Nanoparticles Synthesized from Apis mellifera Honey.

Green approaches for nanoparticle synthesis have emerged as biocompatible, economical, and environment-friendly alternatives to counteract the menace of microbial drug resistance. Recently, the utilization of honey as a green source to synthesize Fe2O3-NPs has been introduced, but its antibacterial activity against one of the opportunistic MDR pathogens, Klebsiella pneumoniae, has not been explored. Therefore, this study employed Apis mellifera honey as a reducing and capping agent for the synthesis of iron oxide nanoparticles (Fe2O3-NPs). Subsequent to the characterization of nanoparticles, their antibacterial, antioxidant, and anti-inflammatory properties were appraised. In UV-Vis spectroscopic analysis, the absorption band ascribed to the SPR peak was observed at 350 nm. XRD analysis confirmed the crystalline nature of Fe2O3-NPs, and the crystal size was deduced to be 36.2 nm. Elemental analysis by EDX validated the presence of iron coupled with oxygen in the nanoparticle composition. In ICP-MS, the highest concentration was of iron (87.15 ppm), followed by sodium (1.49 ppm) and other trace elements (<1 ppm). VSM analysis revealed weak magnetic properties of Fe2O3-NPs. Morphological properties of Fe2O3-NPs revealed by SEM demonstrated that their average size range was 100-150 nm with a non-uniform spherical shape. The antibacterial activity of Fe2O3-NPs was ascertained against 30 clinical isolates of Klebsiella pneumoniae, with the largest inhibition zone recorded being 10 mm. The MIC value for Fe2O3-NPs was 30 µg/mL. However, when mingled with three selected antibiotics, Fe2O3-NPs did not affect any antibacterial activity. Momentous antioxidant (IC50 = 22 µg/mL) and anti-inflammatory (IC50 = 70 µg/mL) activities of Fe2O3-NPs were discerned in comparison with the standard at various concentrations. Consequently, honey-mediated Fe2O3-NP synthesis may serve as a substitute for orthodox antimicrobial drugs and may be explored for prospective biomedical applications.

Cadmium cardiotoxicity is associated with oxidative stress and upregulated TLR-4/NF-kB pathway in rats; protective role of agomelatine.

Cardiotoxicity is one of the hazardous effects of the exposure to the heavy metal cadmium (Cd). Inflammation and oxidative injury are implicated in the cardiotoxic mechanism of Cd. The melatonin receptor agonist agomelatine (AGM) showed promising effects against oxidative and inflammatory responses. This study evaluated the effect of AGM on Cd-induced cardiotoxicity in rats, pointing to its modulatory effect on TLR-4/NF-kB pathway and HSP70. Rats received AGM for 14 days and a single dose of Cd on day 7 and blood and heart samples were collected for analyses. Cd increased serum CK-MB, AST and LDH and caused cardiac tissue injury. Cardiac malondialdehyde (MDA), nitric oxide (NO) and MPO were elevated and GSH, SOD and GST decreased in Cd-administered rats. AGM ameliorated serum CK-MB, AST and LDH and cardiac MDA, NO and MPO, prevented tissue injury and enhanced antioxidants. AGM downregulated serum CRP and cardiac TLR-4, NF-kB, iNOS, IL-6, TNF-α and COX-2 in Cd-administered rats. HSP70 was upregulated in the heart of Cd-challenged rats treated with AGM. In silico findings revealed the binding affinity of AGM with TLR-4 and NF-kB. In conclusion, AGM protected against Cd cardiotoxicity by preventing myocardial injury and oxidative stress and modulating HSP70 and TLR-4/NF-kB pathway.

Synthesis and Characterization of Methoxy-Exfoliated Montmorillonite Nanosheets as Potential Carriers of 5-Fluorouracil Drug with Enhanced Loading, Release, and Cytotoxicity Properties.

Natural bentonite clay (BE) underwent modification steps that involved the exfoliation of its layers into separated nanosheets (EXBE) and further functionalization of these sheets with methanol, forming methoxy-exfoliated bentonite (Mth/EXBE). The synthetically modified products were investigated as enhanced carriers of 5-fluorouracil as compared to raw bentonite. The modification process strongly induced loading properties that increased to 214.4 mg/g (EXBE) and 282.6 mg/g (Mth/EXBE) instead of 124.9 mg/g for bentonite. The loading behaviors were illustrated based on the kinetic (pseudo-first-order model), classic isotherm (Langmuir model), and advanced isotherm modeling (monolayer model of one energy). The Mth/EBE carrier displays significantly higher loading site density (95.9 mg/g) as compared to EXBE (66.2 mg/g) and BE (44.9 mg/g). The loading numbers of 5-Fu in each site of BE, EXBE, and Mth/EXBE (>1) reflect the vertical orientation of these loaded ions involving multi-molecular processes. The loading processes that occurred appeared to be controlled by complex physical and weak chemical mechanisms, considering both Gaussian energy (<8 KJ/mol) as well as loading energy (<40 KJ/mol). The releasing patterns of EXBE and Mth/EXBE exhibit prolonged and continuous properties up to 100 h, with Mth/EXBE displaying much faster behaviors. Based on the release kinetic modeling, the release reactions exhibit non-Fickian transport release properties, validating cooperative diffusion and erosion release mechanisms. The cytotoxicity of 5-Fu is also significantly enhanced by these carriers: 5-Fu/BE (8.6% cell viability), 5-Fu/EXBE (2.21% cell viability), and 5-Fu/Mth/EXBE (0.73% cell viability).