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[
Antioxidants (Basel),
2019]
The objective was to evaluate the toxicity of zinc- and doxycycline-loaded polymeric nanoparticles (NPs) using <i>Caenorhabditis elegans</i> as a model organism. These NPs are composed of ethylene glycol dimethacrylate, 2-hydroxyethyl methacrylate and methacrylic acid. NPs were loaded with doxycycline (D-NPs) and zinc (Zn-NPs) by chemical adsorption, and loading efficacy was demonstrated. Worm death rate in a concentration-response curve basis was calculated for lethality. Metabolism was evaluated through pharyngeal pumping assay. Body length measurements, brood size and egg lays were used to gauge growth, reproduction and fertility respectively. Intracellular hydrogen peroxide levels were determined to assess the reactive oxygen species production. One-way ANOVA and Bonferroni were used for comparisons (<i>p</i> < 0.05). Tested NPs at the highest dosage did not affect lethality or worm metabolism, expressed in terms of death rate and pharyngeal pumping per minute, respectively. Zn-NPs slightly increased worm growth. The concentration of the intracellular hydrogen peroxide levels was the lowest in the D-NPs group. The distinct NPs and concentrations employed were shown to be non-toxic for in situ administration of zinc and doxycycline, reducing the harmful effects of these compounds.
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Romero-Marquez JM, Cianciosi D, Sanchez-Gonzalez C, Quiles JL, Sumalla-Cano S, Navarro-Hortal MD, Battino M, Llopis J, Giampieri F, Esteban-Munoz A, Rivas-Garcia L
[
Food Chem,
2021]
Bioactive compounds from strawberries have been associated with multiple healthy benefits. The present study aimed to assess chemical characterization of a methanolic extract of the Romina strawberry variety in terms of antioxidant capacity, polyphenols profile and chemical elements content. Additionally, potential toxicity, the effect on amyloid-beta production and oxidative stress of the extract was in vivo evaluated in the experimental model Caenorhabditis elegans. Results revealed an important content in phenolic compounds (mainly ellagic acid and pelargonidin-3-glucoside) and minerals (K, Mg, P and Ca). The treatment with 100, 500 or 1000 ug/mL of strawberry extract did not show toxicity. On the contrary, the extract was able to delay amyloid beta-protein induced paralysis, reduced amyloid-beta aggregation and prevented oxidative stress. The potential molecular mechanisms present behind the observed results explored by RNAi technology revealed that DAF-16/FOXO and SKN-1/NRF2 signaling pathways were, at least partially, involved.
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Garcia-Garcia A, Romero-Marquez JM, Rojas S, Choquesillo-Lazarte D, Navarro-Hortal MD, Rivas-Garcia L, Rodriguez-Dieguez A, Quiles JL, Lopez O, Fernandez-Bolanos JG, Salinas-Castillo A
[
Chem Commun (Camb),
2022]
A new palladium coordination compound based on gliclazide with the chemical formula [Pd(glz)2] (where glz = gliclazide) has been synthesized and characterised. The structural characterization reveals that this material consists of mononuclear units formed by a Pd2+ ion coordinated to two molecules of the glz ligand, in which palladium ions exhibit a distorted plane-square coordination sphere. This novel material behaves like a good and selective inhibitor of butyrylcholinesterase, one of the most relevant therapeutic targets against Alzheimer's disease. Analysis of the enzyme kinetics showed a mixed mode of inhibition, the title compound being capable of interacting with both the free enzyme and the enzyme-substrate complex. Finally, the palladium compound shows promising protective activity against Aβ-induced toxicity in the Caenorhabditis elegans model, which has never been reported.
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Shimono K, Honda N, Hasegawa T, Takahashi M, Hashimoto N, Sudo Y, Hayashi S, Mizutani K, Miyauchi S, Yamamoto M, Takagi S, Yamashita K, Tsukamoto T, Murata T
[
J Biol Chem,
2016]
Thermophilic rhodopsin (TR) is a photoreceptor protein with an extremely high thermal stability and the first characterized light-driven electrogenic proton pump derived from the extreme thermophile Thermus thermophilus JL-18. In this study, we confirmed its high thermal stability compared with other microbial rhodopsins and also report the potential availability of TR for optogenetics as a light-induced neural silencer. The x-ray crystal structure of TR revealed that its overall structure is quite similar to that of xanthorhodopsin, including the presence of a putative binding site for a carotenoid antenna; but several distinct structural characteristics of TR, including a decreased surface charge and a larger number of hydrophobic residues and aromatic-aromatic interactions, were also clarified. Based on the crystal structure, the structural changes of TR upon thermal stimulation were investigated by molecular dynamics simulations. The simulations revealed the presence of a thermally induced structural substate in which an increase of hydrophobic interactions in the extracellular domain, the movement of extracellular domains, the formation of a hydrogen bond, and the tilting of transmembrane helices were observed. From the computational and mutational analysis, we propose that an extracellular LPGG motif between helices F and G plays an important role in the thermal stability, acting as a "thermal sensor." These findings will be valuable for understanding retinal proteins with regard to high protein stability and high optogenetic performance.
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Munoz-Ollero P, Navarro-Hortal MD, Esteban-Munoz A, Sanchez-Gonzalez C, Romero-Marquez JM, Tutusaus K, Battino M, Giampieri F, Quiles JL, Forbes-Hernandez TY, Jimenez-Trigo V, Llopis J, Rivas-Garcia L
[
Food Funct,
2022]
Alzheimer's is a chronic degenerative disease of the central nervous system considered the leading cause of dementia in the world. It is characterized by two etiopathological events related to oxidative stress: the aggregation of β-amyloid peptide and the formation of neurofibrillary tangles of hyperphosphorylated Tau protein in the brain. The incidence of this disease increases with age and has been associated with inadequate lifestyles. Some natural compounds have been shown to improve the hallmarks of the disease. However, despite its potential, there is no scientific evidence about Manuka honey (MH) in this regard. In the present work we evaluated the effect of MH on the toxicity induced by Aβ aggregation and Tau in a Caenorhabditis elegans model. Our results demonstrated that MH was able to improve indicators of oxidative stress and delayed Aβ-induced paralysis in the AD model CL4176 through HSP-16.2 and SKN-1/NRF2 pathways. Nevertheless, its sugar content impaired the indicators of locomotion (an indicator of tau neurotoxicity) in both the transgenic strain BR5706 and in the wild-type N2 worms.