In this contribution, poly(maleic acid)-grafted cross-linked chitosan/montmorillonite composite nanospheres (PMAL-CTS/MMT) were synthesized via a facile approach for adsorption of organic dyes. The ...adsorption capacity of PMAL-CTS/MMT towards anionic acid yellow-17 (AY17) and cationic brilliant green (BG) was compared to PMAL-CTS, CTS/MMT, and MMT to emphasize the role of surface functional groups introduced by poly(maleic acid) and montmorillonite. Interestingly, the adsorption efficiency of PMAL-CTS/MMT nanocomposite towards both dyes in the single and binary systems was extremely high due to plenty of functional groups. The affinity of PMAL-CTS/MMT towards cationic and anionic dyes resulted from the feasible modulation of the surface charges as a function of the solution pH. The PMAL-CTS/MMT nanocomposite exhibited a maximum adsorption capacity of 518 and 1910 mg g–1 for AY17 and BG, respectively, which is higher than most of the adsorbents reported in recent literature studies. The proposed mechanism based on the characterization of PMAL-CTS/MMT after the adsorption highlighted that the adsorption is mainly controlled by electrostatic interaction, π − π interactions, and hydrogen bonding. More importantly, the PMAL-CTS/MMT nanocomposite was successfully applied to separate the AY17 and BG dyes from real-life aquatic environments. Collectively, the simple fabrication and superior adsorption performance reveal that PMAL-CTS/MMT has the potential to treat concomitant organic dyes effectively.
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•Poly(maleic acid)-grafted cross-linked chitosan/montmorillonite nanospheres for dye removal.•Controlling the surface charges of the adsorbent as a function of solution pH.•Maximum adsorption capacity of 518 and 1910 mg g–1 for acid yellow-17 and brilliant green, respectively.•Excellent adsorption of cationic and anionic dyes in simulated real-life aquatic environments.
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Alzheimer’s disease (AD) is one of the most common neurodegenerative diseases in which the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/protein kinase B (PKB or Akt) pathway ...is deregulated in response to phosphatase and tensin homolog (PTEN) overexpression. Lactoferrin (LF), a multifunctional iron-binding glycoprotein, is involved in AD pathology; however, direct evidence of its impact upon AD remains unclear. To elucidate LF’s role in AD, the possible protective mechanism post-LF administration for 3 months was investigated in AD patients by observing changes in the p-Akt/PTEN pathway. AD patients showed decreased serum acetylcholine (ACh), serotonin (5-HT), antioxidant and anti-inflammatory markers, and decreased expression of Akt in peripheral blood lymphocytes (PBL), as well as PI3K, and p-Akt levels in PBL lysate; all these parameters were significantly improved after daily LF administration for 3 months. Similarly, elevated serum amyloid β (Aβ) 42, cholesterol, oxidative stress markers, IL-6, heat shock protein (HSP) 90, caspase-3, and p-tau, as well as increased expression of tau, MAPK1 and PTEN in AD patients, were significantly reduced upon LF intake. Improvement in the aforementioned AD surrogate markers post-LF treatment was reflected in enhanced cognitive function assessed by the Mini-Mental State Examination (MMSE) and Alzheimer's Disease Assessment Scale-Cognitive Subscale 11-item (ADAS-COG 11) questionnaires as clinical endpoints. These results provide a basis for a possible protective mechanism of LF in AD through its ability to alleviate the AD pathological cascade and cognitive decline via modulation of the p-Akt/PTEN pathway, which affects the key players of inflammation and oxidative stress that are involved in AD pathology.
As a nutritional supplement, coenzyme Q10 (CoQ10) was tested previously in several models of diabetes and/or insulin resistance (IR); however, its exact mechanisms have not been profoundly ...explicated. Hence, the objective of this work is to verify some of the possible mechanisms that underlie its therapeutic efficacy. Moreover, the study aimed to assess the potential modulatory effect of CoQ10 on the antidiabetic action of glimebiride. An insulin resistance/type 2 diabetic model was adopted, in which rats were fed high fat/high fructose diet (HFFD) for 6 weeks followed by a single sub-diabetogenic dose of streptozotocin (35 mg/kg, i.p.). At the end of the 7(th) week animals were treated with CoQ10 (20 mg/kg, p.o) and/or glimebiride (0.5 mg/kg, p.o) for 2 weeks. CoQ10 alone opposed the HFFD effect and increased the hepatic/muscular content/activity of tyrosine kinase (TK), phosphatidylinositol kinase (PI3K), and adiponectin receptors. Conversely, it decreased the content/activity of insulin receptor isoforms, myeloperoxidase and glucose transporters (GLUT4; 2). Besides, it lowered significantly the serum levels of glucose, insulin, fructosamine and HOMA index, improved the serum lipid panel and elevated the levels of glutathione, sRAGE and adiponectin. On the other hand, CoQ10 lowered the serum levels of malondialdehyde, visfatin, ALT and AST. Surprisingly, CoQ10 effect surpassed that of glimepiride in almost all the assessed parameters, except for glucose, fructosamine, TK, PI3K, and GLUT4. Combining CoQ10 with glimepiride enhanced the effect of the latter on the aforementioned parameters.
These results provided a new insight into the possible mechanisms by which CoQ10 improves insulin sensitivity and adjusts type 2 diabetic disorder. These mechanisms involve modulation of insulin and adiponectin receptors, as well as TK, PI3K, glucose transporters, besides improving lipid profile, redox system, sRAGE, and adipocytokines. The study also points to the potential positive effect of CoQ10 as an adds- on to conventional antidiabetic therapies.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
•Coating CdS QDs with chitosan improve the material biocompability.•Loading sesamol into CdS@CTS.•Improve stability and decrease IC50 of sesamol for cancer cells treatment.
Natural products continued ...to be the treasure trove for the discovery of anticancer drugs. The activity of certain natural products significantly increased with the use of novel drug delivery systems (DDS). Aiming to improve the activity of a natural cytotoxic agent; Sesamol, it was loaded onto cadmium sulfide (CdS) quantum dots (QDs) modified chitosan (CTS). The formed complex Sesamol-CdS@CTS was characterized using X-ray diffraction, UV-Vis absorption spectroscopy, thermogravimetric analysis, dynamic light scattering, Zeta-potential, Fourier transform infrared spectroscopy, fluorescence emission, high resolution transmission electron microscopy, and selected area electron diffraction. The concentration effect of Cd2+ and chitosan on the particle size of CdS QDs was investigated. The cytotoxic activity assay showed that Sesamol-CdS@CTS was more effective against cancer cells compared to the drug alone. The results showed that the half maximal inhibitory concentration values (IC50) of CdS@CTS, Sesamol, and Sesamol-CdS@CTS were 1730 ± 54, 495 ± 16.4, and 117 ± 3.2 μg/mL, respectively. Our results indicated that CdS@CTS exhibited high loading efficiency, and can be used for drug delivery.
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•BS extract inhibits the accumulation of β amyloid and p-tau.•It decreases ChE and caspase-3 activity in brain of T2D rats.•It increases hippocampal suppressed expression of glutamate ...receptors.•It enhances sensitivity of insulin receptors and reduces hippocampal elevated cytokines and oxidative stress.
Type 2 diabetes (T2D) is associated with accelerated cognitive decline. To date, there is no T2D-specific treatment to prevent or ameliorate cognitive dysfunction. Boswellia serrate (BS) gum has been shown to possess multiple pharmacological actions including anti-inflammatory, anticancer and ant- apoptotic actions. The present study was aimed to investigate the effect of BS on cognitive impairment associated with T2D induced in rats by high fat/high fructose (HF/HFr) diet with a single injection of streptozotocin (STZ) and to explore the mechanism of action. The effect of 3 doses of BS extract and the reference drug on the behavioral, biochemical, histopathological and glutamate gene expression abnormalities in T2D rates was evaluated. HF/HFr diet/ STZ induces learning and memory deficits, which were reversed by BS extract. It showed a significant decrease in Aβ deposits and p-tau positive cells. BS extract also reduced significantly the hippocampal elevated levels of caspase-3, cholinesterase (ChE), GSK-3β, TNF-α, IL-1β, IL-6, and MDA. Moreover, BS extract enhanced significantly the suppressed hippocampal level of GSH, SOD and glutamate receptor expression (GluR, NR1, NR2 A, and NR2B). In addition, BS extract alleviated insulin resistance and hyperlipidemia of T2D rats. Our findings suggest that BS extract reversed learning and memory impairment in HF/ HFr diet / STZ induced diabetic rats. This effect may be attributed to the inhibition of insulin resistance, pro-inflammatory cytokines, oxidative stress and hyperlipidemia
This paper proposes a self-adaptive Equilibrium Optimizer (self-EO) to perform better global, combinatorial, engineering, and multi-objective optimization problems. The new self-EO algorithm ...integrates four effective exploring phases, which address the potential shortcomings of the original EO. We validate the performances of the proposed algorithm over a large spectrum of optimization problems, i.e., ten functions of the CEC’20 benchmark, three engineering optimization problems, two combinatorial optimization problems, and three multi-objective problems. We compare the self-EO results to those obtained with nine other metaheuristic algorithms (MAs), including the original EO. We employ different metrics to analyze the results thoroughly. The self-EO analyses suggest that the self-EO algorithm has a greater ability to locate the optimal region, a better trade-off between exploring and exploiting mechanisms, and a faster convergence rate to (near)-optimal solutions than other algorithms. Indeed, the self-EO algorithm reaches better results than the other algorithms for most of the tested functions.
•An enhanced algorithm called the self-EO that employs three strategies is proposed.•Self-EO efficiency and performance are verified on several benchmarks.•CEC’20 suite and 3 engineering problems are used for algorithm validation.•Two combinatorial problems, and ten CEC’20 multi-objective problems are solved.•Self-EO performance is analyzed with many metrics and compared to 30 algorithms.
Nano-silicon application is an efficient novel approach to mitigate the deleterious impacts of drought stress on field crops, which is expected to increase owing to climate change, especially in arid ...regions. Two-season field studies investigated the influence of foliar-applied nano-silicon (0.5, 1, and 1.5 mM) on physiological and biochemical attributes and their impacts on crop water productivity (CWP) and the agronomic traits of faba beans (
Vicia faba
). The plants were evaluated under two irrigation regimes: well-watered (100% ETc giving 406 mm ha
−1
) and drought stress (65% ETc giving 264 mm ha
−1
). It was found that drought stress significantly decreased gas exchange (leaf net photosynthetic rate, stomatal conductance, and rate of transpiration), water relations (relative water content and membrane stability index), nutrient uptake (N, P, K
+
, and Ca
+2
), flavonoids, and phenolic content. In contrast, drought stress significantly increased oxidative stress (H
2
O
2
and
O
2
·
-
) and enzymatic and non-enzymatic antioxidant activities compared with the well-watered treatment. These influences of drought stress were negatively reflected in seed yield-related traits and CWP. However, foliar treatment with nano-silicon, particularly with 1.5 mM, limited the devastating impact of drought stress and markedly enhanced all the aforementioned parameters. Therefore, exogenously applied nano-silicon could be used to improve the CWP and seed and biological yields of faba bean plants under conditions with low water availability in arid environments.
In our pursuit of enhancing acne treatment while minimizing side effects, we developed tailored Adapalene microsponges (MS) optimized using a Box-Behnken design 3
. The independent variables, ...Eudragit RS100 percentage in the polymer mixture, organic phase volume, and drug to polymer percentage, were explored. The optimized formulation exhibited remarkable characteristics, with a 98.3% ± 1.6 production yield, 97.3% ± 1.64 entrapment efficiency, and a particle size of 31.8 ± 1.1 µm. Notably, it achieved a 24 h cumulative drug release of 75.1% ± 1.4. To delve deeper into its efficacy, we evaluated the optimized microspongeal-gel in vitro, in vivo, and clinically. It demonstrated impressive retention in the pilosebaceous unit, a target for acne treatment. Comparative studies between our optimized Adapalene microspongeal gel and marketed Adapalene revealed superior performance. In vivo studies on Propionibacterium acnes-infected mice ears showed a remarkable 97% reduction in ear thickness, accompanied by a significant decrease in inflammatory signs and NF-κB levels, as confirmed by histopathological and histochemical examination. Moreover, in preliminary clinical evaluation, it demonstrated outstanding effectiveness in reducing comedonal lesions while causing fewer irritations. This not only indicates its potential for clinical application but also underscores its ability to enhance patient satisfaction, paving the way for future commercialization.
Iron overload can result in grave consequences in thalassemic patients, despite the availability of iron chelators. Therefore, alternative pathways aiming to reduce iron toxicity are currently ...investigated. Among which, reduction of iron absorption through control of hepcidin production appears to be promising. In this study, we investigated growth differentiation factor-15 (GDF15) and erythroferrone (ERFE) as potential suppressors of hepcidin.
This cross-sectional study was conducted on 61 thalassemic patients and 60 healthy controls. The frequency of GDF15 gene polymorphism (rs4808793) (-3148C/G), serum level of GDF15 and erythroferrone were measured and correlated with those of hepcidin and serum ferritin.
The presence of GDF15 gene mutations were significantly higher in the patients' group compared to controls (P value 0.035). Also, thalassemia patients had significantly higher levels of GDF15 and ERFE and lower hepcidin levels than controls (P value < 0.001). Serum hepcidin level showed significantly negative correlations with GDF15, ERFE, reticulocyte count, LDH level, and serum ferritin. Contrarily, it had highly significant positive correlation with hemoglobin.
High level of GDF15 and/or ERFE may inhibit hepcidin production and increase iron load in patients with thalassemia; therefore, medications that suppress their actions may provide new therapeutic potentials for iron toxicity.
Iron overload continues to be a major contributor to high morbidity and mortality in patients with thalassemia. New strategies together with proper chelation, need to be developed to minimize the effect of iron toxicity. Growth differentiation factor-15 (GDF15) and erythroferrone (ERFE) inhibit hepcidin production and increase iron levels in conditions with ineffective erythropoiesis. Medications that suppress the production or interfere with the action of GDF15 or ERFE may represent new therapeutic potentials for iron toxicity. Prevention of iron toxicity will significantly reduce morbidity and mortality and improve the quality of life of thalassemia patients.
Unlike other widely known Aloe species used for treatment of rheumatoid arthritis, this species suffers from a lack of sufficient studies on its biological and chemical characters. This is what drove ...us to perform this work to evaluate the in vivo anti-arthritic potential of its leaf ethanolic extract. The in vivo anti-arthritic activity of the leaf ethanolic extract at 100 and 200 mg/kg/day b.wt. was evaluated alone and in combination with methotrexate (MTX) using complete Freund’s adjuvant. Serum levels of rheumatoid factor, anti-cyclic citrullinated peptide (anti-CCP), cytokines pro-inflammatory marker, inflammatory mediator serum levels, and oxidative stress mediators were analyzed, in addition to liver function. Orientin, isoorientin, β-sitosterol, its palmitate and its glucoside were isolated. The combined therapy of MTX and the leaf ethanolic extract (especially at 200 mg/kg b.wt.) group showed better activity compared to MTX alone. Moreover, the combined therapy provided additional benefits in lowering the liver toxicity by comparison to MTX alone. We concluded that a synergetic combination of the leaf ethanolic extract and MTX is beneficial in the management of rheumatoid arthritis with fewer side effects on liver function, as well as the possibility of the leaf extract to stand alone as an effective natural anti-arthritic agent.
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