RÉSUMÉ
Alzheimer's disease (AD) is the fifth leading cause of death in older adults, and treatment options are severely lacking. Recent findings demonstrate a strong relationship between skeletal muscle and cognitive function, with evidence supporting that muscle quality and cognitive function are positively correlated in older adults. Conversely, decreased muscle function is associated with a threefold increased risk of cognitive decline. Based on these observations, the purpose of this study was to investigate the negative effects of muscle disuse [via a model of hindlimb immobilization (HLI)] on hippocampal insulin sensitivity and mitochondrial function and identify the potential mechanisms involved. HLI for 10 days in 4-mo-old female Wistar rats resulted in the following novel findings: 1) hippocampal insulin resistance and deficits in whole body glucose homeostasis, 2) dramatically increased mitochondrial reactive oxygen species (ROS) production in the hippocampus, 3) elevated markers for amyloidogenic cleavage of amyloid precursor protein (APP) and tau protein in the hippocampus, 4) and reduced brain-derived neurotrophic factor (BDNF) expression. These findings were associated with global changes in iron homeostasis, with muscle disuse producing muscle iron accumulation in association with decreased serum and whole brain iron levels. We report the novel finding that muscle disuse alters brain iron homeostasis and reveal a strong negative correlation between muscle and brain iron content. Overall, HLI-induced muscle disuse has robust negative effects on hippocampal insulin sensitivity and ROS production in association with altered brain iron homeostasis. This work provides potential novel mechanisms that may help explain how loss of muscle function contributes to cognitive decline and AD risk.NEW & NOTEWORTHY Muscle disuse via hindlimb immobilization increased oxidative stress and insulin resistance in the hippocampus. These findings were in association with muscle iron overload in connection with iron dysregulation in the brain. Overall, our work identifies muscle disuse as a contributor to hippocampal dysfunction, potentially through an iron-based muscle-brain axis, highlighting iron dysregulation as a potential novel mechanism in the relationship between muscle health, cognitive function, and Alzheimer's disease risk.
Sujet(s)
Facteur neurotrophique dérivé du cerveau , Suspension des membres postérieurs , Hippocampe , Insulinorésistance , Mitochondries , Muscles squelettiques , Rat Wistar , Espèces réactives de l'oxygène , Animaux , Insulinorésistance/physiologie , Femelle , Espèces réactives de l'oxygène/métabolisme , Hippocampe/métabolisme , Rats , Mitochondries/métabolisme , Muscles squelettiques/métabolisme , Facteur neurotrophique dérivé du cerveau/métabolisme , Fer/métabolisme , Précurseur de la protéine bêta-amyloïde/métabolisme , Protéines tau/métabolismeRÉSUMÉ
This experiment was conducted to determine the effect of an adsorbent material based on powdered alfalfa leaves added in the aflatoxin B1 (AFB1)-contaminated diet of turkey poults on production parameters, blood cell count, serum biochemistry, liver enzymes, and liver histology. For this purpose, three hundred and fifty female Nicholas-700 poults were randomly assigned into five treatments: (1) Control, AFB1-free diet; (2) AF, diet contaminated with 250 ng AFB1/g; (3) Alfalfa, AFB1-free diet + 0.5% (w/w) adsorbent; (4) AF+alfalfa, diet contaminated with 250 ng AFB1/g + 0.5% (w/w) adsorbent, and (5) AF+ yeast cell wall (YCW), diet contaminated with 250 ng AFB1/g + 0.5% (w/w) of yeast cell wall (a commercial mycotoxin binder used as reference material). The in vivo efficacy of powdered alfalfa leaves was assessed during a 28-day period. In general, the addition of powdered alfalfa leaves in the AFB1-free diet gave the best performance results (body weight, body weight gain, and feed intake) and improved the values of total protein, glucose, calcium, creatinine, and blood urea nitrogen. Moreover, the addition of powdered alfalfa leaves in the AFB1-contaminated diet enhanced body weight and body weight gain and significantly reduced the feed intake, compared to the AF and AF+YCW groups. Additionally, significant alterations in serum parameters were observed in poults intoxicated with the AFB1, compared to the Control group. Furthermore, typical histopathological lesions were observed in the liver of the AF group, which were significantly ameliorated with the addition of powdered alfalfa leaves. Conclusively, these results pointed out that low inclusion of powdered alfalfa leaves in the contaminated feed counteracted the adverse effects of AFB1 in turkey poults.
Sujet(s)
Aflatoxine B1 , Aliment pour animaux , Medicago sativa , Feuilles de plante , Dindons , Animaux , Aflatoxine B1/toxicité , Medicago sativa/composition chimique , Feuilles de plante/composition chimique , Aliment pour animaux/analyse , Femelle , Foie/effets des médicaments et des substances chimiques , Foie/anatomopathologie , Régime alimentaire/médecine vétérinaire , Poudres , Poids/effets des médicaments et des substances chimiquesRÉSUMÉ
[This corrects the article DOI: 10.3389/fvets.2023.1276754.].
RÉSUMÉ
This study aims to evaluate the efficacy of humic acid (HA) from worm compost as an adsorbent for aflatoxin B1 (AFB1) in turkey poults. The experiment involved the inclusion of 0.25% (w/w) HA in the diet of turkey poults consuming aflatoxin-contaminated feed (250 ng AFB1/g). A total of 350 1-day-old female Nicholas-700 turkey poults were randomly allocated to five equal groups: negative control (basal diet); positive control (basal diet + 250 ng AFB1/g; HA (basal diet + 0.25% HA); HA + AFB1 (basal diet + HA + 250 ng AFB1/g); and zeolite + AFB1 (basal diet + 0.25% zeolite + 250 ng AFB1/g). Each group had seven replicates of 10 poults (n = 70). The impact of HA addition was evaluated in terms of performance parameters, relative organ weights, liver histological lesions, and serum biochemical and hematological constituents. In general, the addition of HA improved body weight (BW), body weight gain (BWG), and feed conversion rate (FCR). Furthermore, HA effectively mitigated the toxic effects caused by AFB1 in the majority of the analyzed variables. The results indicated that HA effectively counteracted the AFB1-induced toxic effects in turkey poults. Based on these findings, it can be concluded that HA is capable of removing AFB1 from the contaminated diet.
RÉSUMÉ
This study aimed to investigate the efficacy of a feed additive containing bentonite and enzymatically hydrolyzed yeast on the intestinal health and growth of newly weaned pigs under chronic dietary exposure to fumonisin and aflatoxin. Newly weaned pigs were randomly allotted to one of four possible treatments: a control diet of conventional corn; a diet of corn contaminated with fumonisin and aflatoxin; a diet of mycotoxin-contaminated corn with 0.2% of feed additive; and a diet of mycotoxin contaminated corn with 0.4% of feed additive. We observed lower average weight gain and average daily feed intake in pigs that were fed only mycotoxin-contaminated corn compared to the control group. Feed additive supplementation linearly increased both average weight gain and feed intake, as well as tumor necrosis factor-alpha. In the jejunum, there was an observed decrease in immunoglobulin A and an increase in claudin-1. Additionally, feed additive supplementation increased the villus height to crypt depth ratio compared to the control. In conclusion, feed additives containing bentonite and enzymatically hydrolyzed yeast could mitigate the detrimental effects of mycotoxins on the growth performance of newly weaned pigs by improving intestinal integrity and positively modulating immune response.
Sujet(s)
Aflatoxines , Fumonisines , Mycotoxines , Suidae , Animaux , Fumonisines/toxicité , Saccharomyces cerevisiae , Bentonite , Aflatoxines/toxicité , Compléments alimentaires/analyse , Régime alimentaire/médecine vétérinaire , Mycotoxines/toxicité , Prise de poids , Aliment pour animaux/analyseRÉSUMÉ
BACKGROUND: Aflatoxins (AFs) are common feed contaminants and are one of the common causes of toxin-related pet food poisoning and recalls. OBJECTIVE: Currently, there are no validated methods for the detection and quantitation of AFs in biological matrices to diagnose AF exposure in live animals. Following a successful intra-laboratory method development to quantify AFB1 and AFM1 in animal urine by HPLC with fluorescence detection (HPLC-FLD), the present study was conducted to extensively evaluate the method performance in an unbiased manner using blinded samples. METHODS: The evaluation included two stages. First, the performance was verified in the method-originating laboratory in a single-laboratory blinded method test (BMT-S) trial followed by a multi-laboratory blinded method test (BMT-M) trial. RESULTS: In both trials, accuracy, repeatability, and reproducibility were satisfactory confirming the relatively good ruggedness and robustness of the method and ensuring that it will perform as expected if used by other laboratories in the future. CONCLUSIONS: We extensively evaluated the performance of a quantitative method to detect AFB1 and AFM1 in animal urine by HPLC-FLD by two different laboratories in two separate BMT-S and BMT-M trials. Both BMT results demonstrated the satisfactory accuracy and precision of the method. It is now available to be adopted by other diagnostic laboratories for purposes of diagnosing AF intoxication in animals. HIGHLIGHTS: A simple urine-based diagnostic test method using HPLC-FLD that originated in a single laboratory now has passed a multi-laboratory evaluation and is now available to be shared with other diagnostic laboratories for purposes of diagnosing AF intoxication in animals so better treatment can be rendered.
Sujet(s)
Aflatoxine B1 , Aflatoxines , Animaux , Aflatoxine B1/analyse , Aflatoxines/analyse , Chromatographie en phase liquide à haute performance/méthodes , Contamination des aliments/analyse , Reproductibilité des résultatsRÉSUMÉ
Lignin-containing nanocelluloses (LNCs) have the properties of both lignin and nanocellulose and could overcome the limits of both individual components in metallic nanoparticle synthesis. However, studies on LNCs are still limited, and the potential of such nanomaterials for metallic nanoparticle synthesis has not been fully unraveled. In this study, monometallic silver, gold nanoparticles, and Ag-Au-AgCl nanohybrids were synthesized in situ utilizing LNCs in a chemical-free approach. The parameters, including Ag+ and Au3+ concentrations as well as [Au3+]/[Ag+] ratios, were investigated for their effects on the nanoparticle synthesis. The characterizations, including UV-vis spectrophotometry, transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), X-ray powder diffraction (XRD), and Fourier transform infrared spectroscopy (FTIR), confirmed the coexistence of Ag, Au, and AgCl while indicating the key role of lignin and oxygen-containing functional groups in the nanoparticle synthesis. The as-synthesized AgNPs-, AuNPs-, and nanohybrids-LNC samples were tested for their antibacterial activities. In comparison to the monometallic AgNPs-LNC sample, nanohybrids-LNC synthesized with 0.063 mM Au3+ loading showed superior antibacterial activities with minimum inhibitory concentrations (MICs) at 5 µg/mL against Gram-positive Staphylococcus aureus and 10 µg/mL against Gram-negative Salmonella typhimurium with controlled Ag+ release. The results indicated that LNCs can be used to synthesize metallic nanoparticles, and the resultant Ag-Au-AgCl nanohybrids were a potent antibacterial agent with reduced environmental impacts.
RÉSUMÉ
OBJECTIVE: Comparison was done between high-performance liquid chromatography (HPLC) and a competitive enzyme-linked immunosorbent assay (ELISA) for detection and quantification of aflatoxin B1 (AFB1) in feed samples. The two procedures were standardized and validated before the actual experiment. Five concentrations (0, 5, 10, 20 and 30 ppb) of feed samples were used for both methods. For the HPLC technique, the samples were extracted in acetonitrile/water (90/10) solution, cleaned-up using solid phase extraction (SPE) column, and derivatized by water/trifluoroacetic acid/glacial acetic acid (35/10/5) solution before instrument analysis. The samples were extracted in 70% methanol for the ELISA technique. RESULTS: The two tests showed very strong linearity with correlation coefficient value of > 0.99 using standard solutions. The mean recovery rate was 92.42% (with relative standard deviation (RSD) of 5.97) and 75.64% (RSD = 34.88) for HPLC and ELISA, respectively. There was no statistically significant difference in recovery rate between the two methods. There was a positive correlation (r = 0.84) between them which indicated that the two techniques can be used to detect and quantify aflatoxin B1 in feed samples. However, there were variations among replicates for the ELISA method, which shows that this method is more applicable for screening purposes.
Sujet(s)
Aflatoxine B1/isolement et purification , Chromatographie en phase liquide à haute performance/normes , Test ELISA/normes , Contamination des aliments/analyse , Zea mays/composition chimique , Acétonitriles/composition chimique , Aliment pour animaux/analyse , Animaux , Chromatographie en phase liquide à haute performance/méthodes , Test ELISA/méthodes , Éthanol/composition chimique , Humains , Reproductibilité des résultats , Sensibilité et spécificité , Extraction en phase solide/méthodes , Solvants/composition chimique , Eau/composition chimiqueRÉSUMÉ
Background: Aflatoxins (AFs) are secondary metabolites of fungi and are one of the causes of toxin-related pet food recalls. An intralaboratory method was previously developed to quantify aflatoxin B1 (AFB1) and aflatoxin M1 (AFM1) in animal liver by HPLC with fluorescence detection. Objective: The aim of this study was to extensively evaluate the method performance with a single-laboratory blinded method test (BMT-S) and a multilaboratory blinded method test (BMT-M). Methods: Blinded tissue samples were prepared by a third-party laboratory and sent out to participating laboratories for both BMT-S and BMT-M. Results: In both tests, participants analyzed blinded samples prepared by an independent laboratory. In the BMT-S, accuracy ranged between 111 and 154% for AFB1 and 113 and 159% for AFM1 within the quantitation range of 0.1-0.5 ng/g. The HorRat values for repeatability ranged between 0.1 and 0.3 for AFB1 and 0.3 and 0.6 for AFM1. In the BMT-M, the interlaboratory accuracy ranged between 77 and 81% for AFB1 and 83 and 85% for AFM1 within the quantitation range of 0.2-10 ng/g. The HorRat values for reproducibility ranged between 0.4 and 0.7 for AFB1 and 0.4 and 0.9 for AFM1. Both recovery and reproducibility were acceptable. Conclusions: BMT-M evaluation demonstrated that the method was suitable for quantitation of aflatoxins B1 and M1 in animal liver between laboratories. Highlights: The BMT-S and BMT-M results demonstrated that the method is rugged and reproducible among the participating laboratories.
Sujet(s)
Aflatoxine B1/analyse , Aflatoxine M1/analyse , Chromatographie en phase liquide à haute performance/méthodes , Foie/composition chimique , Animaux , Fluorescence , Reproductibilité des résultatsRÉSUMÉ
Mycotoxins negatively impact animal health. Aflatoxins (AFs) are the most common mycotoxins affecting both large and small animals and are a common cause of toxin-related pet food recalls. Definitive diagnosis of aflatoxicosis is constrained by a lack of validated ante-mortem analytical methods for detection and quantitation of AFs and their metabolites in biological specimens. Herein, we developed and evaluated a urine-based quantitative method for measurement of aflatoxin B1 (AFB1) and its metabolites aflatoxin M1 (AFM1) and aflatoxin Q1 (AFQ1) in animal urine. (Some of the results have been presented at 59th AAVLD conference, Greensboro, North Carolina, October 13-19th, 2016.) This method uses an immuno-affinity column for clean-up and pre-column derivatization followed by high performance liquid chromatography analysis with fluorescence detection. The method has high selectivity, recovery (>81%) and sensitivity with an instrument limit of detection of 0.20-1.02 pg; instrument limit of quantitation of 0.77-4.46 pg; and a method lower limit of quantitation of 0.30-2.5 ng/mL. The method has high accuracy, repeatability, and is rugged against minor changes. However, because of poor sensitivity of AFQ1 at low concentrations we recommend this method for quantitative determination of AFB1 and AFM1, and for qualitative measurement of AFQ1 in animal urine for diagnosis of aflatoxicosis.
Sujet(s)
Aflatoxines/urine , Aflatoxine B1/urine , Aflatoxine M1/urine , Animaux , Chromatographie en phase liquide à haute performance , Fluorescence , Examen des urinesRÉSUMÉ
Nematode parasites infect â¼2 billion people world-wide. Infections are treated and prevented by anthelmintic drugs, some of which act on nicotinic acetylcholine receptors (nAChRs). There is an unmet need for novel therapeutic agents because of concerns about the development of resistance. We have selected Asu-ACR-16 from a significant nematode parasite genus, Ascaris suum, as a pharmaceutical target and nicotine as our basic moiety (EC50 6.21 ± 0.56 µM, Imax 82.39 ± 2.52%) to facilitate the development of more effective anthelmintics. We expressed Asu-ACR-16 in Xenopus oocytes and used two-electrode voltage clamp electrophysiology to determine agonist concentration-current-response relationships and determine the potencies (EC50s) of the agonists. Here, we describe the synthesis of a novel agonist, (S)-5-ethynyl-anabasine, and show that it is more potent (EC50 0.14 ± 0.01 µM) than other nicotine alkaloids on Asu-ACR-16. Agonists acting on ACR-16 receptors have the potential to circumvent drug resistance to anthelmintics, like levamisole, that do not act on the ACR-16 receptors.
Sujet(s)
Anabasine/analogues et dérivés , Ascaris suum/métabolisme , Agonistes nicotiniques/pharmacologie , Récepteurs nicotiniques/métabolisme , Anabasine/synthèse chimique , Anabasine/métabolisme , Anabasine/pharmacologie , Animaux , Ascaris suum/génétique , Découverte de médicament , Lévamisole/pharmacologie , Agonistes nicotiniques/synthèse chimique , Agonistes nicotiniques/composition chimique , Agonistes nicotiniques/isolement et purification , Ovocytes , Xenopus/génétiqueRÉSUMÉ
Tandem reactions involving Rh-catalyzed intermolecular hydroacylations of alkynes with salicylaldehydes followed by intramolecular oxo-Michael additions are described for the diastereoselective synthesis of 2,3-disubstituted chroman-4-ones. The tandem hydroacylation/oxo-Michael additions occur to form 2,3-disubstituted chroman-4-ones in high yields from a range of 1,2-disubstituted acetylenes and substituted salicylaldehyes. The resulting 2,3-disubstituted chroman-4-ones are readily fluorinated to form trans-3-fluoro-2,3-disubstituted chroman-4-ones in high yields with excellent diastereoselectivity.
Sujet(s)
Alcynes/composition chimique , 4H-1-Benzopyran-4-ones/synthèse chimique , Hydrocarbures fluorés/synthèse chimique , Rhodium/composition chimique , Aldéhydes/composition chimique , Catalyse , 4H-1-Benzopyran-4-ones/composition chimique , Halogénation , Hydrocarbures fluorés/composition chimique , Structure moléculaire , StéréoisomérieRÉSUMÉ
Catalytic, enantioselective hydroacylations of N-allylindole-2-carboxaldehydes and N-allylpyrrole-2-carboxaldehydes are reported. In contrast to many alkene hydroacylations that form six-membered rings, these annulative processes occur in the absence of ancillary functionality to stabilize the acylrhodium(III) hydride intermediate. The intramolecular hydroacylation reactions generate 7,8-dihydropyrido[1,2-a]indol-9(6H)ones and 6,7-dihydroindolizin-8(5H)-ones in moderate to high yields with excellent enantioselectivities.
Sujet(s)
Aldéhydes/composition chimique , Alcènes/composition chimique , Composés hétérocycliques/composition chimique , Composés hétérocycliques/synthèse chimique , Cétones/synthèse chimique , Azote/composition chimique , Rhodium/composition chimique , Catalyse , Chélateurs/composition chimique , Cétones/composition chimique , Structure moléculaire , StéréoisomérieRÉSUMÉ
A simple and straightforward method for the preparation of indole-3-carboxylic acids was discovered through the direct carboxylation of indoles with atmospheric pressure of carbon dioxide (CO(2)) under basic conditions. The key for the reaction was found to be the use of a large excess of LiO(t)Bu as a base to suppress the undesired decarboxylation side reaction.
RÉSUMÉ
The gold-catalyzed tandem cyclization of 1,2-bis(alkynyl)-2-en-1-ones with indoles offers an efficient and straightforward route to indole-fused polycyclic systems. The process is realized through a cascade carbonyl-yne cyclization/Friedel-Crafts/indole-yne cyclization sequence catalyzed by a single-pot catalyst of gold.
Sujet(s)
Alcynes/composition chimique , Or/composition chimique , Indoles/synthèse chimique , Catalyse , Cyclisation , Indoles/composition chimique , Structure moléculaireRÉSUMÉ
An efficient access to N-phth pyrrroles via gold-catalyzed cycloisomerization of N-phth alkynylaziridines has been described. Functionalized pyrroles including pyrrole-2-carboxylates or 2-pyrrolyl ketone are easily constructed in generally good yields by this method. The resulting pyrroles can be further converted to N-amino pyrrole or 2-acyl pyrrole, which are important synthetic intermediates for amplification of molecular complexity.