Although dietary antibiotic growth promoters have long been used to increase growth performance in commercial food animal production, the biochemical details associated with these effects remain poorly defined. A metabolomics approach was used to characterize and identify the biochemical compounds present in the intestine of broiler chickens fed a standard, unsupplemented diet or a diet supplemented with the antibiotic growth promoters, virginiamycin or bacitracin methylene disalicylate. Compared with unsupplemented controls, the levels of 218 biochemicals were altered (156 increased, 62 decreased) in chickens given the virginiamycin-supplemented diet, while 119 were altered (96 increased, 23 decreased) with the bacitracin-supplemented diet. When compared between antibiotic-supplemented groups, 79 chemicals were altered (43 increased, 36 decreased) in virginiamycin- vs. bacitracin-supplemented chickens. The changes in the levels of intestinal biochemicals provided a distinctive biochemical signature unique to each antibiotic-supplemented group. These biochemical signatures were characterized by increases in the levels of metabolites of amino acids (e.g. 5-hydroxylysine, 2-aminoadipate, 5-hydroxyindoleaceate, 7-hydroxyindole sulfate), fatty acids (e.g. oleate/vaccenate, eicosapentaenoate, 16-hydroxypalmitate, stearate), nucleosides (e.g. inosine, N⁶-methyladenosine), and vitamins (e.g. nicotinamide). These results provide the framework for future studies to identify natural chemical compounds to improve poultry growth performance without the use of in-feed antibiotics.

Accumulation of the parkin-interacting substrate (PARIS; ZNF746), due to inactivation of parkin, contributes to Parkinson’s disease (PD) through repression of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α; PPARGC1A) activity. Here, we identify farnesol as an inhibitor of PARIS. Farnesol promoted the farnesylation of PARIS, preventing its repression of PGC-1α via decreasing PARIS occupancy on the PPARGC1A promoter. Farnesol prevented dopaminergic neuronal loss and behavioral deficits via farnesylation of PARIS in PARIS transgenic mice, ventral midbrain transduction of AAV-PARIS, adult conditional parkin KO mice, and the α-synuclein preformed fibril model of sporadic PD. PARIS farnesylation is decreased in the substantia nigra of patients with PD, suggesting that reduced farnesylation of PARIS may play a role in PD. Thus, farnesol may be beneficial in the treatment of PD by enhancing the farnesylation of PARIS and restoring PGC-1α activity.

The present study was conducted to evaluate the encapsulated essential oils (EEO) as an alternative to anticoccidials using a coccidiosis vaccine challenged model in broiler chickens. A total of 600 one-day-old male broiler chicks were provided with no added corn/soybean-meal-based control diet or diets that contained either salinomycin (SAL) or thymol- and carvacrol-based EEO at 60 and 120 mg per kg of diet. Before challenge at 21 days, each treatment had 10 replicates except for the no-added control group, which had 20 replicates. On day 21, half of the control groups were orally challenged with a coccidiosis vaccine at 25 times higher than the recommended vaccine dose. During 22 to 28 days (i.e., one-week post coccidiosis vaccine challenge), the challenged chickens had a decrease (P < 0.05) in body weight gain and feed intake but an increase in feed conversion ratio compared with the non-challenged, naïve control chickens. However, dietary EEO significantly counteracted (P < 0.05) coccidiosis-vaccine-induced depression in body weight gain and feed intake. Inclusion of dietary EEO linearly decreased (P < 0.05) the concentrations of the volatile fatty acids. Dietary SAL and EEO affected gut morphology in chickens at 20 days post-hatch. Dietary EEO linearly (P = 0.073) increased serum catalase activity as the inclusion level increased. Collectively, our study shows that dietary EEO increased coccidiosis-vaccine-induced growth depression and altered gut physiology in broiler chickens. Our study adds to the accumulating evidence that dietary EEO is proven to be an effective alternative to anticoccidials for broiler chickens.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by the loss of upper and lower motor neurons, which eventually may lead to death. Critical to the mission of developing effective therapies for ALS is the discovery of biomarkers that can illuminate mechanisms of neurodegeneration and have diagnostic, prognostic, or pharmacodynamic value. Here, we merged unbiased discovery-based approaches and targeted quantitative comparative analyses to identify proteins that are altered in cerebrospinal fluid (CSF) from patients with ALS. Mass spectrometry (MS)-based proteomic approaches employing tandem mass tag (TMT) quantification methods from 40 CSF samples comprising 20 patients with ALS and 20 healthy control (HC) individuals identified 53 proteins that are differential between the two groups after CSF fractionation. Notably, these proteins included both previously identified ones, validating our approach, and novel ones that have the potential for expanding biomarker repertoire. The identified proteins were subsequently examined using parallel reaction monitoring (PRM) MS methods on 61 unfractionated CSF samples comprising 30 patients with ALS and 31 HC individuals. Fifteen proteins (APOB, APP, CAMK2A, CHI3L1, CHIT1, CLSTN3, ERAP2, FSTL4, GPNMB, JCHAIN, L1CAM, NPTX2, SERPINA1, SERPINA3, and UCHL1) showed significant differences between ALS and the control. Taken together, this study identified multiple novel proteins that are altered in ALS, providing the foundation for developing new biomarkers for ALS.