Correction: Atuahene et al. A Supplement with Bromelain, Lentinula edodes, and Quercetin: Antioxidant Capacity and Effects on Morphofunctional and Fecal Parameters (Calprotectin, Cortisol, and Intestinal Fermentation Products) in Kennel Dogs. Vet. Sci. 2023, 10, 486.

There was an error in the original publication [...].

A Supplement with Bromelain, Lentinula edodes, and Quercetin: Antioxidant Capacity and Effects on Morphofunctional and Fecal Parameters (Calprotectin, Cortisol, and Intestinal Fermentation Products) in Kennel Dogs.

Oxidative stress causes several pathological conditions in humans and animals, including gastrointestinal disorders. The aim of this study was to analyze the antioxidant capacity of three natural powdered raw materials containing quercetin, bromelain, and Lentinula edodes and develop a new feed supplement for dogs using a combination of them. The total phenolic content (TPC), antioxidant activity, DPPH (2,2-diphenyl-1-picrylhydrazyl), and ABTS (2,2'-Azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt) of the extracts, either individually or in combination, were evaluated colorimetrically. The effects of this supplement on healthy adult dogs' nutritional, inflammatory, and stress status were evaluated. American Staffordshire Terrier adult female dogs (n = 30) were randomly assigned to a control (n = 15) or a treated (n = 15) group. The supplement was added as powder to the food of the treated dogs once daily for 28 days. There was no significant difference in the body weight and body condition scores between the initial and final phases of the experiment. At the end of our study, a significant decrease in fecal calprotectin, cortisol, indole/skatole, and N-methylhistamine and a significant increase in short-chain fatty acids were observed as compared to the control group. In conclusion, this natural feed supplement can be used to improve gastrointestinal health and psycho-physical conditions in dogs.

Amaranthus hypochondriacus L. as a Sustainable Source of Nutrients and Bioactive Compounds for Animal Feeding.

With the aim to explore the use of A. hypochondriacus seeds for animal feeding, the agronomic traits, nutrients, and bioactive compounds of four accessions with different origin (India, Nebraska, Iowa, and Pennsylvania) grown in a Mediterranean environment were studied. Proximate composition was determined using the official methods of analyses, fatty acid profile by gas chromatography, total phenolic content (TPC) and the scavenging activity (DPPH• and ABTS•+) by colorimetric method. A one-way ANOVA model was performed to determine the differences between accessions. The four A. hypochondriacus accessions showed interesting seed yield results. No significant differences were observed for crude protein and crude fiber; the oil content showed the significant highest values in the seeds from Nebraska and Pennsylvania, but their nutritional characteristics were significantly different. The accession from Nebraska showed the highest oleic and linoleic acid levels, the highest values of polyunsaturated fatty acids, the best atherogenic and thrombogenic indices and hypocholesterolemic/hypercholesterolaemic ratio, and the highest TPC content. The accession from Pennsylvania showed the highest antioxidant activity and lowest peroxidation index. On the whole, A. hypochondriacus seeds can be used as pseudo-cereal to balance the animal diet and the accession should be chosen according to the different metabolic pathways of unsaturated fatty acids in ruminant and monogastric animals.

Productive and Qualitative Traits of Amaranthus Cruentus L.: An Unconventional Healthy Ingredient in Animal Feed.

Agronomic traits, oil content, fatty acid composition, antioxidant activity, and total phenolic content were studied on eight A. cruentus accessions cultivated in Southern Italy. A one-way ANOVA model was performed to compare accessions and the Principal Components Analysis was applied to identify patterns in our dataset and highlight similarities and differences. A. cruentus showed valuable seed yield (0.27 kg/m2, on average) comparable to the main tradition cereals used for animal feeding. Seed-oil composition showed significant differences among the accessions. Data showed a higher lipid content than most cereal grains (from 5.6 to 7.3%). Approximately 60% of fatty acids were unsaturated; linoleic fatty acid ranged from 19 to 34%, oleic acid from 29 to 36%, and alfa-linolenic fatty acid from 0.3 to 0.5%, respectively. The saturated/unsaturated fatty acid ratio ranged from 0.5 to 0.8, the hypocholesterolemic:hypercholesterolaemic ratio from 1.7 to 2.7, the Atherogenic Index from 0.38 to 0.66, the Thrombogenic Index from 0.85 to 1.48, the total phenolic content from 0.14 to 0.36 mg/g seeds, and the antioxidant activity (DPPH•) from 0.30 to 0.50. The studied seed-oil composition evidenced A. cruentus as a healthy ingredient for animal feed and consequently, as a possible substitute for traditional cereals. Accessions from Mexico and Arizona emerged for their high qualitative traits.

Hydroxytriazole derivatives as potent and selective aldo-keto reductase 1C3 (AKR1C3) inhibitors discovered by bioisosteric scaffold hopping approach.

The aldo-keto reductase 1C3 isoform (AKR1C3) plays a vital role in the biosynthesis of androgens, making this enzyme an attractive target for castration-resistant prostate cancer therapy. Although AKR1C3 is a promising drug target, no AKR1C3-targeted agent has to date been approved for clinical use. Flufenamic acid, a non-steroidal anti-inflammatory drug, is known to potently inhibit AKR1C3 in a non-selective manner as COX off-target effects are also observed. To diminish off-target effects, we have applied a scaffold hopping strategy replacing the benzoic acid moiety of flufenamic acid with an acidic hydroxyazolecarbonylic scaffold. In particular, differently N-substituted hydroxylated triazoles were designed to simultaneously interact with both subpockets 1 and 2 in the active site of AKR1C3, larger for AKR1C3 than other AKR1Cs isoforms. Through computational design and iterative rounds of synthesis and biological evaluation, novel compounds are reported, sharing high selectivity (up to 230-fold) for AKR1C3 over 1C2 isoform and minimal COX1 and COX2 off-target inhibition. A docking study of compound 8, the most interesting compound of the series, suggested that its methoxybenzyl substitution has the ability to fit inside subpocket 2, being involved in π-π staking interaction with Trp227 (partial overlapping) and in a T-shape π-π staking with Trp86. This compound was also shown to diminish testosterone production in the AKR1C3-expressing 22RV1 prostate cancer cell line while synergistic effect was observed when 8 was administered in combination with abiraterone or enzalutamide.

Development of an Acrylate Derivative Targeting the NLRP3 Inflammasome for the Treatment of Inflammatory Bowel Disease.

Pharmacological inhibition of NLRP3 inflammasome activation may offer a new option in the treatment of inflammatory bowel disease. In this work, we report the design, synthesis, and biological screening of a series of acrylate derivatives as NLRP3 inhibitors. The in vitro determination of reactivity, cytotoxicity, NLRP3 ATPase inhibition, and antipyroptotic properties allowed the selection of 11 (INF39), a nontoxic, irreversible NLRP3 inhibitor able to decrease interleukin-1ß release from macrophages. Bioluminescence resonance energy transfer experiments proved that this compound was able to directly interfere with NLRP3 activation in cells. In vivo studies confirmed the ability of the selected lead to alleviate the effects of colitis induced by 2,4-dinitrobenzenesulfonic acid in rats after oral administration.

Design and synthesis of N-benzoyl amino acid derivatives as DNA methylation inhibitors.

The inhibition of human DNA Methyl Transferases (DNMT) is a novel promising approach to address the epigenetic dysregulation of gene expression in different diseases. Inspired by the validated virtual screening hit NSC137546, a series of N-benzoyl amino acid analogues was synthesized and obtained compounds were assessed for their ability to inhibit DNMT-dependent DNA methylation in vitro. The biological screening allowed the definition of a set of preliminary structure-activity relationships and the identification of compounds promising for further development. Among the synthesized compounds, L-glutamic acid derivatives 22, 23, and 24 showed the highest ability to prevent DNA methylation in a total cell lysate. Compound 22 inhibited DNMT1 and DNMT3A activity in a concentration-dependent manner in the micromolar range. In addition, compound 22 proved to be stable in human serum and it was thus selected as a starting point for further biological studies.

Design, Synthesis, and Evaluation of Acrylamide Derivatives as Direct NLRP3 Inflammasome Inhibitors.

NLRP3 inflammasome plays a key role in the intracellular activation of caspase-1, processing of pro-inflammatory interleukin-1ß (IL-1ß), and pyroptotic cell death cascade. The overactivation of NLRP3 is implicated in the pathogenesis of autoinflammatory diseases, known as cryopyrin-associated periodic syndromes (CAPS), and in the progression of several diseases, such as atherosclerosis, type-2 diabetes, gout, and Alzheimer's disease. In this study, the synthesis of acrylamide derivatives and their pharmaco-toxicological evaluation as potential inhibitors of NLRP3-dependent events was undertaken. Five hits were identified and evaluated for their efficiency in inhibiting IL-1ß release from different macrophage subtypes, including CAPS mutant macrophages. The most attractive hits were tested for their ability to inhibit NLRP3 ATPase activity on human recombinant NLRP3. This screening allowed the identification of 14, 2-(2-chlorobenzyl)-N-(4-sulfamoylphenethyl)acrylamide, which was able to concentration-dependently inhibit NLRP3 ATPase with an IC50 value of 74 µm. The putative binding pose of 14 in the ATPase domain of NLRP3 was also proposed.