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.

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.

Insight into the Morphological Properties of Nano-Kaolinite (Nanoscrolls and Nanosheets) on Its Qualification as Delivery Structure of Oxaliplatin: Loading, Release, and Kinetic Studies.

Natural kaolinite underwent advanced morphological-modification processes that involved exfoliation of its layers into separated single nanosheets (KNs) and scrolled nanoparticles as nanotubes (KNTs). Synthetic nanostructures have been characterized as advanced and effective oxaliplatin-medication (OXAP) delivery systems. The morphological-transformation processes resulted in a remarkable enhancement in the loading capacity to 304.9 mg/g (KNs) and 473 mg/g (KNTs) instead of 29.6 mg/g for raw kaolinite. The loading reactions that occurred by KNs and KNTs displayed classic pseudo-first-order kinetics (R2 > 0.90) and conventional Langmuir isotherms (R2 = 0.99). KNTs exhibit a higher active site density (80.8 mg/g) in comparison to KNs (66.3 mg/g) and raw kaolinite (6.5 mg/g). Furthermore, compared to KNs and raw kaolinite, each site on the surface of KNTs may hold up to six molecules of OXAP (n = 5.8), in comparison with five molecules for KNs. This was accomplished by multi-molecular processes, including physical mechanisms considering both the Gaussian energy (<8 KJ/mol) and the loading energy (<40 KJ/mol). The release activity of OXAP from KNs and KNTs exhibits continuous and regulated profiles up to 100 h, either by KNs or KNTs, with substantially faster characteristics for KNTs. Based on the release kinetic investigations, the release processes have non-Fickian transport-release features, indicating cooperative-diffusion and erosion-release mechanisms. The synthesized structures have a significant cytotoxicity impact on HCT-116 cancer cell lines (KNs (71.4% cell viability and 143.6 g/mL IC-50); KNTs (11.3% cell viability and 114.3 g/mL IC-50). Additionally, these carriers dramatically increase OXAP's cytotoxicity (2.04% cell viability, 15.4 g/mL IC-50 (OXAP/KNs); 0.6% cell viability, 4.5 g/mL IC-50 (OXAP/KNTs)).

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).

Insights into the Effect of Chitosan and ß-Cyclodextrin Hybridization of Zeolite-A on Its Physicochemical and Cytotoxic Properties as a Bio-Carrier for 5-Fluorouracil: Equilibrium and Release Kinetics Studies.

Synthetic zeolite-A (ZA) was hybridized with two different biopolymers (chitosan and ß-cyclodextrin) producing biocompatible chitosan/zeolite-A (CS/ZA) and ß-cyclodextrin/zeolite-A (CD/ZA) biocomposites. The synthetic composites were assessed as bio-carriers of the 5-fluorouracil drug (5-Fu) with enhanced properties, highlighting the impact of the polymer type. The hybridization by the two biopolymers resulted in notable increases in the 5-Fu loading capacities, to 218.2 mg/g (CS/ZA) and 291.3 mg/g (CD/ZA), as compared to ZA (134.2 mg/g). The loading behaviors using ZA as well as CS/ZA and CD/ZA were illustrated based on the classic kinetics properties of pseudo-first-order kinetics (R2 > 0.95) and the traditional Langmuir isotherm (R2 = 0.99). CD/ZA shows a significantly higher active site density (102.7 mg/g) in comparison to CS/ZA (64 mg/g) and ZA (35.8 mg/g). The number of loaded 5-Fu per site of ZA, CS/ZA, and CD/ZA (>1) validates the vertical ordering of the loaded drug ions by multi-molecular processes. These processes are mainly physical mechanisms based on the determined Gaussian energy (<8 kJ/mol) and loading energy (<40 kJ/mol). Both the CS/ZA and CD/ZA 5-Fu release activities display continuous and controlled profiles up to 80 h, with CD/ZA exhibiting much faster release. According to the release kinetics studies, the release processes contain non-Fickian transport release properties, suggesting cooperative diffusion and erosion release mechanisms. The cytotoxicity of 5-Fu is also significantly enhanced by these carriers: 5-Fu/ZA (11.72% cell viability), 5-Fu/CS/ZA (5.43% cell viability), and 5-Fu/CD/ZA (1.83% cell viability).

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.

Genes and Longevity of Lifespan.

Aging is a complex process indicated by low energy levels, declined physiological activity, stress induced loss of homeostasis leading to the risk of diseases and mortality. Recent developments in medical sciences and an increased availability of nutritional requirements has significantly increased the average human lifespan worldwide. Several environmental and physiological factors contribute to the aging process. However, about 40% human life expectancy is inherited among generations, many lifespan associated genes, genetic mechanisms and pathways have been demonstrated during last decades. In the present review, we have evaluated many human genes and their non-human orthologs established for their role in the regulation of lifespan. The study has included more than fifty genes reported in the literature for their contributions to the longevity of life. Intact genomic DNA is essential for the life activities at the level of cell, tissue, and organ. Nucleic acids are vulnerable to oxidative stress, chemotherapies, and exposure to radiations. Efficient DNA repair mechanisms are essential for the maintenance of genomic integrity, damaged DNA is not replicated and transferred to next generations rather the presence of deleterious DNA initiates signaling cascades leading to the cell cycle arrest or apoptosis. DNA modifications, DNA methylation, histone methylation, histone acetylation and DNA damage can eventually lead towards apoptosis. The importance of calorie restriction therapy in the extension of lifespan has also been discussed. The role of pathways involved in the regulation of lifespan such as DAF-16/FOXO (forkhead box protein O1), TOR and JNK pathways has also been particularized. The study provides an updated account of genetic factors associated with the extended lifespan and their interactive contributory role with cellular pathways.

Multifarious roles of mTOR signaling in cognitive aging and cerebrovascular dysfunction of Alzheimer's disease.

Age-related cognitive failure is a main devastating incident affecting even healthy people. Alzheimer's disease (AD) is the utmost common form of dementia among the geriatric community. In the pathogenesis of AD, cerebrovascular dysfunction is revealed before the beginning of the cognitive decline. Mounting proof shows a precarious impact of cerebrovascular dysregulation in the development of AD pathology. Recent studies document that the mammalian target of rapamycin (mTOR) acts as a crucial effector of cerebrovascular dysregulation in AD. The mTOR contributes to brain vascular dysfunction and subsequence cerebral blood flow deficits as well as cognitive impairment. Furthermore, mTOR causes the blood-brain barrier (BBB) breakdown in AD models. Inhibition of mTOR hyperactivity protects the BBB integrity in AD. Furthermore, mTOR drives cognitive defect and cerebrovascular dysfunction, which are greatly prevalent in AD, but the central molecular mechanisms underlying these alterations are obscure. This review represents the crucial and current research findings regarding the role of mTOR signaling in cognitive aging and cerebrovascular dysfunction in the pathogenesis of AD.

Revisiting the Amyloid Cascade Hypothesis: From Anti-Aß Therapeutics to Auspicious New Ways for Alzheimer's Disease.

Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder related to age, characterized by the cerebral deposition of fibrils, which are made from the amyloid-ß (Aß), a peptide of 40-42 amino acids. The conversion of Aß into neurotoxic oligomeric, fibrillar, and protofibrillar assemblies is supposed to be the main pathological event in AD. After Aß accumulation, the clinical symptoms fall out predominantly due to the deficient brain clearance of the peptide. For several years, researchers have attempted to decline the Aß monomer, oligomer, and aggregate levels, as well as plaques, employing agents that facilitate the reduction of Aß and antagonize Aß aggregation, or raise Aß clearance from brain. Unluckily, broad clinical trials with mild to moderate AD participants have shown that these approaches were unsuccessful. Several clinical trials are running involving patients whose disease is at an early stage, but the preliminary outcomes are not clinically impressive. Many studies have been conducted against oligomers of Aß which are the utmost neurotoxic molecular species. Trials with monoclonal antibodies directed against Aß oligomers have exhibited exciting findings. Nevertheless, Aß oligomers maintain equivalent states in both monomeric and aggregation forms; so, previously administered drugs that precisely decrease Aß monomer or Aß plaques ought to have displayed valuable clinical benefits. In this article, Aß-based therapeutic strategies are discussed and several promising new ways to fight against AD are appraised.

Combination Drug Therapy for the Management of Alzheimer's Disease.

Alzheimer's disease (AD) is the leading cause of dementia worldwide. Even though the number of AD patients is rapidly growing, there is no effective treatment for this neurodegenerative disorder. At present, implementation of effective treatment approaches for AD is vital to meet clinical needs. In AD research, priorities concern the development of disease-modifying therapeutic agents to be used in the early phases of AD and the optimization of the symptomatic treatments predominantly dedicated to the more advanced AD stages. Until now, available therapeutic agents for AD treatment only provide symptomatic treatment. Since AD pathogenesis is multifactorial, use of a multimodal therapeutic intervention addressing several molecular targets of AD-related pathological processes seems to be the most practical approach to modify the course of AD progression. It has been demonstrated through numerous studies, that the clinical efficacy of combination therapy (CT) is higher than that of monotherapy. In case of AD, CT is more effective, mostly when started early, at slowing the rate of cognitive impairment. In this review, we have covered the major studies regarding CT to combat AD pathogenesis. Moreover, we have also highlighted the safety, tolerability, and efficacy of CT in the treatment of AD.

The Toxicological Aspects of the Heat-Borne Toxicant 5-Hydroxymethylfurfural in Animals: A Review.

The incidence of adverse reactions in food is very low, however, some food products contain toxins formed naturally due to their handling, processing and storage conditions. 5-(Hydroxymethyl)-2-furfural (HMF) can be formed by hydrogenation of sugar substances in some of manufactured foodstuffs and honey under elevated temperatures and reduced pH conditions following Maillard reactions. In previous studies, it was found that HMF was responsible for harmful (mutagenic, genotoxic, cytotoxic and enzyme inhibitory) effects on human health. HMF occurs in a wide variety of food products like dried fruit, juice, caramel products, coffee, bakery, malt and vinegar. The formation of HMF is not only an indicator of food storage conditions and quality, but HMF could also be used as an indicator of the potential occurrence of contamination during heat-processing of some food products such as coffee, milk, honey and processed fruits. This review focuses on HMF formation and summarizes the adverse effects of HMF on human health.

Effects of the dietary inclusion of a probiotic or prebiotic on florfenicol pharmacokinetic profile in broiler chicken.

We evaluated the effect of prebiotic or probiotic as feed additives on florfenicol kinetic in broilers feed. Unsexed two hundred, thirty-five-day-old broiler chickens, were put in four equal groups (n = 50). The first group was administrated florfenicol intravenous at 30 mg/kg body weight (BW) only once dosage without pre- or probiotic administration to determine the bioavailability. While, the second group was administrated florfenicol (intracrop routes; a dosage of 30 mg/kg BW for five progressive days) without pre- or probiotic co-administration. The third and the fourth groups were administrated the same dose of florfenicol (intracrop route) for five successive days, followed by 10 days of prebiotic or probiotic treatment respectively. The plasma florfenicol % was identified by high-pressure liquid chromatography (HPLC) after the first florfenicol administration (intravenous or intracrop routes) in all groups. Then, the residual levels of florfenicol were determined in liver, kidney and muscle tissues from the second, third and fourth groups which were exposed to florfenicol orally. Our results demonstrated that broilers pre-treated with prebiotic or probiotic significantly increased Cmax , AUC0- t , AUC0-inf as well as AUMC values, while significant drop was recorded in V/F and CL/F. Prebiotic or probiotic influenced the cumulative effect of florfenicol in liver and kidney tissues of treated birds.

Chicoric acid prevents methotrexate-induced kidney injury by suppressing NF-κB/NLRP3 inflammasome activation and up-regulating Nrf2/ARE/HO-1 signaling.

OBJECTIVE: Chicoric acid (CA) is a natural product with promising antioxidant and anti-inflammatory properties; however, its protective effect on methotrexate (MTX)-induced acute kidney injury (AKI) hasn't been reported. We investigated the effect of CA on MTX-induced AKI in rats, pointing to the role of NF-κB/NLRP3 inflammasome and Nrf2/ARE/HO-1 signaling. MATERIALS AND METHODS: Wistar rats received 25 mg/kg and 50 mg/kg CA for 15 days and a single injection of MTX at day 16. At day 19, the rats were killed, and samples were collected for analyses. RESULTS: MTX induced a significant increase in serum creatinine and urea, and kidney Kim-1, reactive oxygen species (ROS), malondialdehyde and nitric oxide levels. In addition, MTX-induced rats exhibited multiple histopathological alterations, diminished antioxidant defenses, and decreased expression of Nrf2, NQO-1 and HO-1. CA prevented histological alterations, ameliorated kidney function markers, attenuated ROS production and lipid peroxidation, and boosted antioxidant defenses. CA suppressed the expression of NF-κB p65, NLRP3, caspase-1 and IL-1ß in the kidney of MTX-induced rats. Furthermore, CA inhibited MTX-induced apoptosis as evidenced by the decreased expression of BAX and caspase-3, and increased Bcl-2 gene expression. CONCLUSIONS: CA prevented MTX-induced AKI through activation of Nrf2/ARE/HO-1 signaling, and attenuation of ROS-induced activation of NF-κB/NLRP3 inflammasome signaling.

Development of Illuminant Glow-in-the-Dark Cotton Fabric Coated by Luminescent Composite with Antimicrobial Activity and Ultraviolet Protection.

The main objective of technical protective clothing is to enhance people safety at work, which may save their life or keep them healthy away against some hazards. We developed a warning cotton fabric with a traffic safety warning photoluminescence character that continues emitting light for a long period of time after the removal of the illuminant source. Rare earth-doped strontium aluminate was dispersed in an aqueous medium of a polyacrylic-based binder to give a cross-linkable photoluminescent formula to be applied onto cotton substrate employing spray-coat approach. To introduce a transparent photoluminescent film, the Rare earth pigment must be fully dispersed to prevent aggregation. The long-persistent photoluminescent layer was deposited on cotton surface employing different concentrations of the rare earth pigment phosphor. The excitation wavelength maximum band of the spray-coated film on cotton fabric was found to occur at 365 nm, while the emission was recorded at 515 nm. Yellowish-green emissive color was monitored by CIE color data under the ultraviolet excitation source. The spray-coated fabric was characterized by wavelength dispersive X-ray fluorescence (WD-XRF), phosphorescence and excitation spectra, elements mapping, scanning electron microscopy (SEM) and energy-dispersive X-ray (EDX). The comfort measurements were studied by exploring both of fabric stiffness and air-permeability. Furthermore, the spray-coated textile substrates displayed good fastness properties and a reversible luminescent glow in the dark.

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.

Dynamic interactions and inhibitory mechanisms of Artemisia annua terpenoids with carbonic anhydrase IX.

This study evaluates the inhibitory potential of terpenoids isolated from Artemisia annua against carbonic anhydrase IX (CAIX), a crucial enzyme overexpressed in hypoxic tumor environments. Employing a multidisciplinary approach, we utilized in vitro assays, enzyme kinetics, molecular docking, and molecular dynamics (MD) simulations to comprehensively assess the efficacy of these compounds. Among the terpenoids tested, manool emerged as the most potent inhibitor, exhibiting the lowest IC50 value of 160.2 ± 15.2 nM. This was followed by labda-8(17),12-diene-15,16-dial with an IC50 of 297.9 ± 8.84 nM. Enzyme kinetics revealed a mixed inhibition mode for both compounds. Molecular docking aligned well with in vitro data, showing extensive polar and hydrophobic interactions within the CAIX binding site. Further insights were gained through 300 ns MD simulations, which highlighted the dynamic interactions and stability of these complexes. Manool demonstrated the most significant stabilization of CAIX, as evidenced by favorable RMSD, Rg, SASA profiles, and the strongest hydrogen bonding interactions. Additionally, MM/PBSA calculations confirmed manool's superior binding affinity. These findings underscore the therapeutic potential of manool as a potent CAIX inhibitor, providing a foundation for the development of effective anticancer agents targeting hypoxic tumor environments. ADMET analysis revealed favorable pharmacokinetic profiles for the terpenoids, with manool demonstrating high lipophilicity and BBB permeability, though potential CYP-mediated interactions were noted.

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.

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.

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.