{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T11:34:34Z","timestamp":1778153674910,"version":"3.51.4"},"reference-count":107,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,4,19]],"date-time":"2023-04-19T00:00:00Z","timestamp":1681862400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Romanian Ministry of Research and Innovation, CCCDI\u2014UEFISCDI","award":["PN-III-P1-1.2-PCCDI-2017-0473\/"],"award-info":[{"award-number":["PN-III-P1-1.2-PCCDI-2017-0473\/"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>Mycotoxins are toxic compounds produced by certain strains of fungi that can contaminate raw feed materials. Once ingested, even in small doses, they cause multiple health issues for animals and, downstream, for people consuming meat. It was proposed that inclusion of antioxidant-rich plant-derived feed might diminish the harmful effects of mycotoxins, maintaining the farm animals\u2019 health and meat quality for human consumption. This work investigates the large scale proteomic effects on piglets\u2019 liver of aflatoxin B1 and ochratoxin A mycotoxins and the potential compensatory effects of grapeseed and sea buckthorn meal administration as dietary byproduct antioxidants against mycotoxins\u2019 damage. Forty cross-bred TOPIGS-40 hybrid piglets after weaning were assigned to three (n = 10) experimental groups (A, M, AM) and one control group (C) and fed with experimental diets for 30 days. After 4 weeks, liver samples were collected, and the microsomal fraction was isolated. Unbiased label-free, library-free, data-independent acquisition (DIA) mass spectrometry SWATH methods were able to relatively quantify 1878 proteins from piglets\u2019 liver microsomes, confirming previously reported effects on metabolism of xenobiotics by cytochrome P450, TCA cycle, glutathione synthesis and use, and oxidative phosphorylation. Pathways enrichment revealed that fatty acid metabolism, steroid biosynthesis, regulation of actin cytoskeleton, regulation of gene expression by spliceosomes, membrane trafficking, peroxisome, thermogenesis, retinol, pyruvate, and amino acids metabolism pathways are also affected by the mycotoxins. Antioxidants restored expression level of proteins PRDX3, AGL, PYGL, fatty acids biosynthesis, endoplasmic reticulum, peroxisome, amino acid synthesis pathways, and, partially, OXPHOS mitochondrial subunits. However, excess of antioxidants might cause significant changes in CYP2C301, PPP4R4, COL18A1, UBASH3A, and other proteins expression levels. Future analysis of proteomics data corelated to animals growing performance and meat quality studies are necessary.<\/jats:p>","DOI":"10.3390\/toxins15040299","type":"journal-article","created":{"date-parts":[[2023,4,20]],"date-time":"2023-04-20T02:01:11Z","timestamp":1681956071000},"page":"299","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Natural Antioxidant By-Product Mixture Counteracts the Effects of Aflatoxin B1 and Ochratoxin A Exposure of Piglets after Weaning: A Proteomic Survey on Liver Microsomal Fraction"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5758-1422","authenticated-orcid":false,"given":"Roua Gabriela","family":"Popescu","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Bucharest, Splaiul Independentei No. 91-95, 050095 Bucharest, Romania"},{"name":"Independent Research Association, Timisului No. 58, 012416 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9429-4502","authenticated-orcid":false,"given":"George C\u0103t\u0103lin","family":"Marinescu","sequence":"additional","affiliation":[{"name":"Independent Research Association, Timisului No. 58, 012416 Bucharest, Romania"},{"name":"Blue Screen SRL, Timisului No. 58, 012416 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andreea Lumini\u021ba","family":"R\u0103dulescu","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Bucharest, Splaiul Independentei No. 91-95, 050095 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniela Eliza","family":"Marin","sequence":"additional","affiliation":[{"name":"Laboratory of Animal Biology, National Institute for Research and Development for Biology and Animal Nutrition, Calea Bucuresti No. 1, 077015 Balotesti, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0727-5827","authenticated-orcid":false,"given":"Ionelia","family":"\u021a\u0103ranu","sequence":"additional","affiliation":[{"name":"Laboratory of Animal Biology, National Institute for Research and Development for Biology and Animal Nutrition, Calea Bucuresti No. 1, 077015 Balotesti, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anca","family":"Dinischiotu","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Bucharest, Splaiul Independentei No. 91-95, 050095 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/bs.afnr.2019.02.007","article-title":"Mycotoxins in food and feed","volume":"Volume 89","year":"2019","journal-title":"Advances in Food and Nutrition Research"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.jfutfo.2022.03.002","article-title":"An overview on the major mycotoxins in food products: Characteristics, toxicity, and analysis","volume":"2","author":"Jebur","year":"2022","journal-title":"J. Futur. Foods"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"K\u0119pi\u0144ska-Pacelik, J., and Biel, W. (2021). Alimentary risk of mycotoxins for humans and animals. Toxins, 13.","DOI":"10.3390\/toxins13110822"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Ne\u0161i\u0107, K., Habschied, K., and Mastanjevi\u0107, K. (2021). Possibilities for the Biological Control of Mycotoxins in Food and Feed. Toxins, 13.","DOI":"10.3390\/toxins13030198"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.foodcont.2014.12.027","article-title":"Survey of aflatoxin B1 and ochratoxin A occurrence in traditional meat products coming from Croatian households and markets","volume":"52","author":"Pleadin","year":"2015","journal-title":"Food Control"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Popescu, R.G., R\u0103dulescu, A.L., Georgescu, S.E., and Dinischiotu, A. (2022). Aflatoxins in Feed: Types, Metabolism, Health Consequences in Swine and Mitigation Strategies. Toxins, 14.","DOI":"10.3390\/toxins14120853"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"111701","DOI":"10.1016\/j.envres.2021.111701","article-title":"Prevalence, level and health risk assessment of mycotoxins in the fried poultry eggs from Jordan","volume":"200","author":"Omar","year":"2021","journal-title":"Environ. Res."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Awuchi, C.G., Ondari, E.N., Nwozo, S., Odongo, G.A., Eseoghene, J., Twinomuhwezi, H., Ogbonna, C.U., Upadhyay, A.K., Adeleye, A.O., and Okpala, C.O.R. (2022). Livestock and Their Associated Health Concerns: A Review. Toxins, 14.","DOI":"10.3390\/toxins14030167"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"23339","DOI":"10.1038\/s41598-021-02822-x","article-title":"Exposure and risk characterizations of ochratoxins A and aflatoxins through maize (Zea mays) consumed in different agro-ecological zones of Ghana","volume":"11","author":"Kortei","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"381","DOI":"10.3109\/1547691X.2012.675365","article-title":"Immunological status of the progeny of breeder hens kept on ochratoxin A (OTA)-and aflatoxin B1 (AFB1)-contaminated feeds","volume":"9","author":"Khan","year":"2012","journal-title":"J. Immunotoxicol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.cofs.2019.08.009","article-title":"Impact of mycotoxin contamination in the animal feed industry","volume":"29","author":"Magnoli","year":"2019","journal-title":"Curr. Opin. Food Sci."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Tsiouris, V., Tassis, P., Raj, J., Mantzios, T., Kiskinis, K., Vasiljevi\u0107, M., Deli\u0107, N., Petridou, E., Brellou, G.D., and Polizopoulou, Z. (2021). Investigation of a novel multicomponent mycotoxin detoxifying agent in amelioration of mycotoxicosis induced by aflatoxin-b1 and ochratoxin a in broiler chicks. Toxins, 13.","DOI":"10.3390\/toxins13060367"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Jin, S., Yang, H., Wang, Y., Pang, Q., Jiao, Y., Shan, A., and Feng, X. (2021). Dietary curcumin alleviated aflatoxin b1-induced acute liver damage in ducks by regulating nlrp3\u2013caspase-1 signaling pathways. Foods, 10.","DOI":"10.3390\/foods10123086"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"122087","DOI":"10.1016\/j.jhazmat.2020.122087","article-title":"Effects of mycotoxin-contaminated feed on farm animals","volume":"389","author":"Yang","year":"2020","journal-title":"J. Hazard. Mater."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Pu, J., Yuan, Q., Yan, H., Tian, G., Chen, D., He, J., Zheng, P., Yu, J., Mao, X., and Huang, Z. (2021). Effects of chronic exposure to low levels of dietary aflatoxin b1 on growth performance, apparent total tract digestibility and intestinal health in pigs. Animals, 11.","DOI":"10.3390\/ani11020336"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Tkaczyk, A., and Jedziniak, P. (2021). Mycotoxin biomarkers in pigs\u2014Current state of knowledge and analytics. Toxins, 13.","DOI":"10.3390\/toxins13080586"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Vlachou, M., Pexara, A., Solomakos, N., and Govaris, A. (2022). Ochratoxin A in Slaughtered Pigs and Pork Products. Toxins, 14.","DOI":"10.3390\/toxins14020067"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Janik, E., Niemcewicz, M., Ceremuga, M., Stela, M., Saluk-bijak, J., Siadkowski, A., and Bijak, M. (2020). Molecular Aspects of Mycotoxins\u2014A Serious Problem for Human Health. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21218187"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.jscs.2010.06.006","article-title":"Impact of mycotoxins on humans and animals","volume":"15","author":"Zain","year":"2011","journal-title":"J. Saudi Chem. Soc."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"112661","DOI":"10.1016\/j.fct.2021.112661","article-title":"Multi-mycotoxin occurrence in feed, metabolism and carry-over to animal-derived food products: A review","volume":"158","author":"Tolosa","year":"2021","journal-title":"Food Chem. Toxicol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Nji, Q.N., Babalola, O.O., Nleya, N., and Mwanza, M. (2022). Underreported Human Exposure to Mycotoxins: The Case of South Africa. Foods, 11.","DOI":"10.3390\/foods11172714"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"104095","DOI":"10.1016\/j.micpath.2020.104095","article-title":"Mycotoxin contamination and control strategy in human, domestic animal and poultry: A review","volume":"142","author":"Haque","year":"2020","journal-title":"Microb. Pathog."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Ahmed, T., and Hashmi, M.Z. (2022). Hazardous Environmental Micro-Pollutants, Health Impacts and Allied Treatment Technologies. Emerging Contaminants and Associated Treatment Technologies, Springer. [1st ed.].","DOI":"10.1007\/978-3-030-96523-5"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Pickova, D., Ostry, V., and Malir, F. (2021). A Recent Overview of Producers and Important Dietary Sources of Aflatoxins. Toxins, 13.","DOI":"10.3390\/toxins13030186"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12896-021-00730-6","article-title":"Enzymatic degradation is an effective means to reduce aflatoxin contamination in maize","volume":"21","author":"Schmidt","year":"2021","journal-title":"BMC Biotechnol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"13158","DOI":"10.1038\/s41598-019-49584-1","article-title":"Aflatoxin levels in maize and peanut and blood in women and children: The case of Timor-Leste","volume":"9","author":"Williams","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2266","DOI":"10.3389\/fmicb.2019.02266","article-title":"Aflatoxins in Food and Feed: An Overview on Prevalence, Detection and Control Strategies","volume":"10","author":"Mahato","year":"2019","journal-title":"Front. Microbiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1016\/j.ijheh.2013.08.007","article-title":"International Journal of Hygiene and Detection of serum AFB 1 -lysine adduct in Malaysia and its association with liver and kidney functions","volume":"217","author":"Redzwan","year":"2014","journal-title":"Int. J. Hyg. Environ. Health"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"103225","DOI":"10.1016\/j.etap.2019.103225","article-title":"Clinical features of a fl atoxin B1-exposed patients with liver cancer and the molecular mechanism of a fl atoxin B1 on liver cancer cells","volume":"71","author":"Zhou","year":"2019","journal-title":"Environ. Toxicol. Pharmacol."},{"key":"ref_30","first-page":"1","article-title":"Aflatoxins: Toxicity, Occurrences and Chronic Exposure","volume":"1","author":"Assaf","year":"2022","journal-title":"Aflatoxins\u2014Occurrence, Detection and Novel Detoxification Strategies"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.toxicon.2020.08.031","article-title":"Toxicon Ochratoxins in food and feed: Occurrence and its impact on human health and management strategies","volume":"187","author":"Kumar","year":"2020","journal-title":"Toxicon"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"152582","DOI":"10.1016\/j.tox.2020.152582","article-title":"Microphysiological system modeling of ochratoxin A-associated nephrotoxicity","volume":"444","author":"Imaoka","year":"2020","journal-title":"Toxicology"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.fct.2018.10.004","article-title":"Renal toxicity through AhR, PXR, and Nrf2 signaling pathway activation of ochratoxin A-induced oxidative stress in kidney cells","volume":"122","author":"Lee","year":"2018","journal-title":"Food Chem. Toxicol."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Li, P., Li, K., Zou, C., Tong, C., Sun, L., Cao, Z., Yang, S., and Lyu, Q. (2020). Selenium yeast alleviates ochratoxin a-induced hepatotoxicity via modulation of the PI3K\/AKT and Nrf2\/Keap1 signaling pathways in chickens. Toxins, 12.","DOI":"10.1155\/2020\/4048706"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1007\/s00210-018-1538-9","article-title":"A comparison between the effects of ochratoxin A and aristolochic acid on the inflammation and oxidative stress in the liver and kidney of weanling piglets","volume":"391","author":"Marin","year":"2018","journal-title":"Naunyn Schmiedebergs Arch Pharmacol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1080\/02652030701567442","article-title":"Impact of mycotoxins on human health in developing countries","volume":"25","author":"Shephard","year":"2008","journal-title":"Food Addit Contam."},{"key":"ref_37","first-page":"1","article-title":"Implications of Mycotoxins in Food Safety","volume":"1","author":"Marc","year":"2022","journal-title":"Mycotoxins and Food Safety\u2014Recent Advances"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1186\/s40104-022-00714-2","article-title":"Nutritional impact of mycotoxins in food animal production and strategies for mitigation","volume":"13","author":"Xu","year":"2022","journal-title":"J. Anim. Sci. Biotechnol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/j.micpath.2018.02.035","article-title":"Post-weaning piglets fed with different levels of fungal mycotoxins and spray-dried porcine plasma have improved weight gain, feed intake and reduced diarrhea incidence","volume":"117","author":"Paiano","year":"2018","journal-title":"Microb. Pathog."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Holanda, D.M., Kim, Y.I., Parnsen, W., and Kim, S.W. (2021). Phytobiotics with Adsorbent to Mitigate Toxicity of Multiple Mycotoxins on Health and Growth of Pigs. Toxins, 13.","DOI":"10.3390\/toxins13070442"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.anifeedsci.2018.01.017","article-title":"Strategies to prevent and reduce mycotoxins for compound feed manufacturing","volume":"237","author":"Peng","year":"2018","journal-title":"Anim. Feed Sci. Technol."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Palade, L.M., Dore, M.I., Marin, D.E., Rotar, M.C., and Taranu, I. (2021). Assessment of Food By-Products\u2019 Potential for Simultaneous Binding of Aflatoxin B1 and Zearalenone. Toxins, 13.","DOI":"10.3390\/toxins13010002"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"84","DOI":"10.2478\/azibna-2021-0007","article-title":"Effect of sea buckthorn meal extract in alleviating the toxic effect of ochratoxin A and zearalenone in porcine peripheral blood mononuclear cells","volume":"24","author":"Marin","year":"2021","journal-title":"Arch. Zootech."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"993834","DOI":"10.3389\/fmicb.2022.993834","article-title":"Natural inhibitors: A sustainable way to combat aflatoxins","volume":"13","author":"Ahmad","year":"2022","journal-title":"Front. Microbiol."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Popescu, R.G., Bulgaru, C., Untea, A., Vlassa, M., Filip, M., Hermenean, A., Marin, D., \u021a\u0103ranu, I., Georgescu, S.E., and Dinischiotu, A. (2021). The Effectiveness of Dietary Byproduct Antioxidants on Induced CYP Genes Expression and Histological Alteration in Piglets Liver and Kidney Fed with Aflatoxin B1 and Ochratoxin, A. Toxins, 13.","DOI":"10.3390\/toxins13020148"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Popescu, R.G., Avramescu, S., Marin, D.E., \u021a\u0103ranu, I., Georgescu, S.E., and Dinischiotu, A. (2021). The reduction of the combined effects of aflatoxin and ochratoxin a in piglet livers and kidneys by dietary antioxidants. Toxins, 13.","DOI":"10.3390\/toxins13090648"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1038\/s41592-019-0638-x","article-title":"DIA-NN: Neural networks and interference correction enable deep proteome coverage in high throughput","volume":"17","author":"Demichev","year":"2020","journal-title":"Nat. Methods"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"152989","DOI":"10.1016\/j.tox.2021.152989","article-title":"Endoplasmic reticulum stress pathway mediates T-2 toxin-induced chondrocyte apoptosis","volume":"464","author":"Liu","year":"2021","journal-title":"Toxicology"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1406","DOI":"10.1080\/10408398.2016.1260526","article-title":"Mechanisms of cell death induction by food-borne mycotoxins","volume":"58","author":"Yin","year":"2018","journal-title":"Crit. Rev. Food. Sci. Nutr."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1007\/s00262-017-1975-1","article-title":"Intratumoral administration of cGAMP transiently accumulates potent macrophages for anti-tumor immunity at a mouse tumor site","volume":"66","author":"Ohkuri","year":"2017","journal-title":"Cancer Immunol. Immunother."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Pollutri, D., and Penzo, M. (2020). Ribosomal Protein L10: From Function to Dysfunction. Cells., 9.","DOI":"10.3390\/cells9112503"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fnsyn.2017.00017","article-title":"Selective Inactivation of Fibroblast Growth Factor 22 (FGF22) in CA3 Pyramidal Neurons Impairs Local Synaptogenesis and Affective Behavior Without Affecting Dentate Neurogenesis","volume":"9","author":"Terauchi","year":"2017","journal-title":"Front. Synaptic Neurosci."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Farooq, M., Khan, A.W., Kim, M.S., and Choi, S. (2021). The role of fibroblast growth factor (FGF) signaling in tissue repair and regeneration. Cells, 10.","DOI":"10.3390\/cells10113242"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"39","DOI":"10.3892\/etm.2020.9166","article-title":"Japanese patients with mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase deficiency: In vitro functional analysis of five novel HMGCS2 mutations","volume":"20","author":"Ago","year":"2020","journal-title":"Exp. Ther. Med."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.tem.2013.09.002","article-title":"Ketone bodies as signaling metabolites","volume":"25","author":"Newman","year":"2014","journal-title":"Trends Endocrinol Metab."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"100295","DOI":"10.1016\/j.jlr.2022.100295","article-title":"The Non Catalytic Protein ERG28 has a Functional Role in Cholesterol Synthesis and is Coregulated Transcriptionally","volume":"63","author":"Fenton","year":"2022","journal-title":"J. Lipid Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"742349","DOI":"10.3389\/fphar.2021.742349","article-title":"Integrated Analysis and Finding Reveal Anti\u2013Liver Cancer Targets and Mechanisms of Pachyman (Poria cocos Polysaccharides)","volume":"12","author":"Qin","year":"2021","journal-title":"Front. Pharmacol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1016\/j.tim.2014.12.003","article-title":"Mx GTPases: Dynamin-like antiviral machines of innate immunity","volume":"23","author":"Haller","year":"2015","journal-title":"Trends Microbiol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/S0925-4773(00)00530-X","article-title":"A gene trap integration provides an early in situ marker for hepatic specification of the foregut endoderm","volume":"100","author":"Watt","year":"2001","journal-title":"Mech. Dev."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"7875","DOI":"10.1074\/jbc.M807827200","article-title":"Identification and functional analysis of a novel cyclin E\/Cdk2 substrate ankrd17","volume":"284","author":"Deng","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1080\/00498254.2022.2148139","article-title":"A comprehensive analysis of six forms of cytochrome P450 2C (CYP2C) in pigs","volume":"52","author":"Uno","year":"2022","journal-title":"Xenobiotica"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1124\/dmd.117.075697","article-title":"Characterization of the Tissue Distribution of the Mouse Cyp2c Subfamily by Quantitative PCR Analysiss","volume":"45","author":"Graves","year":"2017","journal-title":"Drug Metab. Dispos."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Lacombe, J., and Ferron, M. (2018). VKORC1L1, an enzyme mediating the effect of vitamin K in liver and extrahepatic tissues. Nutrients, 10.","DOI":"10.3390\/nu10080970"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1583","DOI":"10.1016\/S0021-9258(19)68073-7","article-title":"Vitamin K-dependent carboxylation. Evidence that at least two microsomal dehydrogenases reduce vitamin K1 to support carboxylation","volume":"257","author":"Wallin","year":"1982","journal-title":"J. Biol. Chem."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"575","DOI":"10.3168\/jds.2020-18503","article-title":"Mitochondrial protein gene expression and the oxidative phosphorylation pathway associated with feed efficiency and energy balance in dairy cattle","volume":"104","author":"Dorji","year":"2021","journal-title":"J. Dairy Sci."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1093\/ps\/85.1.8","article-title":"Feed efficiency and mitochondrial function","volume":"85","author":"Bottje","year":"2006","journal-title":"Poult. Sci."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"100009","DOI":"10.1016\/j.animal.2020.100009","article-title":"Effect of dietary restriction and subsequent realimentation on hepatic oxidative phosphorylation in cattle","volume":"15","author":"Keogh","year":"2021","journal-title":"Animal"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"4366","DOI":"10.1038\/s41598-019-40579-6","article-title":"Cationic gold nanoparticles elicit mitochondrial dysfunction: A multi-omics study","volume":"9","author":"Gallud","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"4401","DOI":"10.1038\/s41598-020-61244-3","article-title":"Downregulation of respiratory complex I mediates major signalling changes triggered by TOR activation","volume":"10","author":"Magnin","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1186\/s40170-021-00275-4","article-title":"Dynamic regulation of mitochondrial pyruvate metabolism is necessary for orthotopic pancreatic tumor growth","volume":"9","author":"Mohan","year":"2021","journal-title":"Cancer Metab."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1038\/s41467-019-13668-3","article-title":"Mitochondrial TCA cycle metabolites control physiology and disease","volume":"11","author":"Chandel","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_72","first-page":"3","article-title":"Bin Mitochondrial electron transport chain, ROS generation and uncoupling (Review)","volume":"44","author":"Zhao","year":"2019","journal-title":"Int. J. Mol. Med."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1016\/j.bbabio.2012.09.009","article-title":"Respiratory chain complex II as general sensor for apoptosis","volume":"1827","author":"Grimm","year":"2013","journal-title":"Biochim. Biophys. Acta Bioenerg."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Luo, Y., Ma, J., and Lu, W. (2020). The significance of mitochondrial dysfunction in cancer. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21165598"},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Silva-Marrero, J.I., S\u00e1ez, A., Caballero-Solares, A., Viegas, I., Almajano, M.P., Fern\u00e1ndez, F., Baanante, I.V., and Met\u00f3n, I. (2017). A transcriptomic approach to study the effect of long-term starvation and diet composition on the expression of mitochondrial oxidative phosphorylation genes in gilthead sea bream (Sparus aurata). BMC Genom., 18.","DOI":"10.1186\/s12864-017-4148-x"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"2493","DOI":"10.1093\/hmg\/ddx144","article-title":"Respiratory chain enzyme deficiency induces mitochondrial location of actin-binding gelsolin to modulate the oligomerization of VDAC complexes and cell survival","volume":"26","author":"Arenas","year":"2017","journal-title":"Hum. Mol. Genet."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"e80919","DOI":"10.7554\/eLife.80919","article-title":"Differential requirements for mitochondrial electron transport chain components in the adult murine liver","volume":"11","author":"Lesner","year":"2022","journal-title":"Elife"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"2105587","DOI":"10.1002\/advs.202105587","article-title":"Hepatic Suppression of Mitochondrial Complex II Assembly Drives Systemic Metabolic Benefits","volume":"9","author":"Wang","year":"2022","journal-title":"Adv. Sci."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1002\/2211-5463.13398","article-title":"Mitochondrial complex IV defects induce metabolic and signaling perturbations that expose potential vulnerabilities in HCT116 cells","volume":"12","author":"Uchenunu","year":"2022","journal-title":"FEBS Open Bio"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"e08501","DOI":"10.1016\/j.heliyon.2021.e08501","article-title":"Changes in TCA cycle and TCA cycle-related metabolites in plasma upon citric acid administration in rats","volume":"7","author":"Hara","year":"2021","journal-title":"Heliyon"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1007\/s13197-019-04077-x","article-title":"Effect of amino acids and their derivatives on meat quality of finishing pigs","volume":"57","author":"Ma","year":"2020","journal-title":"J. Food Sci. Technol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"971479","DOI":"10.3389\/fonc.2022.971479","article-title":"Targeting oxidative phosphorylation as an approach for the treatment of ovarian cancer","volume":"12","author":"Wu","year":"2022","journal-title":"Front. Oncol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"127","DOI":"10.3389\/fphys.2019.00127","article-title":"Reciprocal regulation of V-ATPase and glycolytic pathway elements in health and disease","volume":"10","author":"Hayek","year":"2019","journal-title":"Front. Physiol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"18891","DOI":"10.18632\/oncotarget.3783","article-title":"Increased expression of fatty acid synthase provides a survival advantage to colorectal cancer cells via upregulation of cellular respiration","volume":"6","author":"Zaytseva","year":"2015","journal-title":"Oncotarget"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"109720","DOI":"10.1016\/j.cbi.2021.109720","article-title":"Quercetin ameliorates ochratoxin A-Induced immunotoxicity in broiler chickens by modulation of PI3K\/AKT pathway","volume":"351","author":"Abdelrahman","year":"2022","journal-title":"Chem. Biol. Interact."},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Yang, M., Ma, F., and Guan, M. (2021). Role of steroid hormones in the pathogenesis of nonalcoholic fatty liver disease. Metabolites, 11.","DOI":"10.3390\/metabo11050320"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.mad.2015.08.007","article-title":"Up-regulation of steroid biosynthesis by retinoid signaling: Implications for aging","volume":"150","author":"Manna","year":"2015","journal-title":"Mech. Ageing Dev."},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Lee, J.M., Lee, H., Kang, S.B., and Park, W.J. (2016). Fatty acid desaturases, polyunsaturated fatty acid regulation, and biotechnological advances. Nutrients, 8.","DOI":"10.3390\/nu8010023"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"2728","DOI":"10.1111\/j.1742-4658.2007.05807.x","article-title":"Metabolic pathway that produces essential fatty acids from polymethylene-interrupted polyunsaturated fatty acids in animal cells","volume":"274","author":"Tanaka","year":"2007","journal-title":"FEBS J."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1186\/s40104-019-0343-8","article-title":"Linoleic acid metabolic pathway allows for an efficient increase of intramuscular fat content in pigs","volume":"10","author":"Gol","year":"2019","journal-title":"J. Anim. Sci. Biotechnol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1080\/01961779308048955","article-title":"Metabolism of Sulfur-Containing Xenobiotics","volume":"13","author":"Mitchell","year":"1993","journal-title":"Sulfur Rep."},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Fujii, J., Homma, T., and Osaki, T. (2022). Superoxide Radicals in the Execution of Cell Death. Antioxidants, 11.","DOI":"10.3390\/antiox11030501"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1186\/s41021-021-00211-4","article-title":"PRDX1 is essential for the viability and maintenance of reactive oxygen species in chicken DT40","volume":"43","author":"Moriwaki","year":"2021","journal-title":"Genes Environ."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"a022616","DOI":"10.1101\/cshperspect.a022616","article-title":"Rab proteins and the compartmentalization of the endosomal system","volume":"6","author":"Zerial","year":"2014","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"e00024-20","DOI":"10.1128\/MMBR.00024-20","article-title":"RidA Proteins Protect against Metabolic Damage by Reactive Intermediates","volume":"84","author":"Irons","year":"2020","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1016\/j.ajhg.2015.02.002","article-title":"Mutations in NDUFB11, encoding a complex i component of the mitochondrial respiratory chain, cause microphthalmia with linear skin defects syndrome","volume":"96","author":"Alawi","year":"2015","journal-title":"Am. J. Hum. Genet."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"24936","DOI":"10.1074\/jbc.C114.581868","article-title":"Assignment of 2\u2032-O-methyltransferases to modification sites on the mammalian mitochondrial large subunit 16 S ribosomal RNA (rRNA)","volume":"289","author":"Lee","year":"2014","journal-title":"J. Biol. Chem."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"908807","DOI":"10.3389\/fgene.2022.908807","article-title":"High Expression of TMEM33 Predicts Poor Prognosis and Promotes Cell Proliferation in Cervical Cancer","volume":"13","author":"Chen","year":"2022","journal-title":"Front. Genet."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"585361","DOI":"10.3389\/fimmu.2020.585361","article-title":"C4b Binding Protein Acts as an Innate Immune Effector Against Influenza A Virus","volume":"11","author":"Varghese","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1038\/sj.embor.7400993","article-title":"The ethics of animal research. Talking Point on the use of animals in scientific research","volume":"8","author":"Festing","year":"2007","journal-title":"EMBO Rep."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1016\/j.tiv.2010.10.007","article-title":"Comparison of cytochrome P450 concentrations and metabolic activities in porcine hepatic microsomes prepared with two different methods","volume":"25","author":"Rasmussen","year":"2011","journal-title":"Toxicol. Vitr."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/0003-2697(76)90527-3","article-title":"A rapid and sensitive for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding","volume":"72","author":"Bradford","year":"1976","journal-title":"Anal. Biochem."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"D543","DOI":"10.1093\/nar\/gkab1038","article-title":"The PRIDE database resources in 2022: A hub for mass spectrometry-based proteomics evidences","volume":"50","author":"Bai","year":"2022","journal-title":"Nucleic Acids Res."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1396","DOI":"10.1074\/mcp.RA119.001777","article-title":"PolySTest: Robust statistical testing of proteomics data with missing values improves detection of biologically relevant features","volume":"19","author":"Hagensen","year":"2020","journal-title":"Mol. Cell. Proteom."},{"key":"ref_105","unstructured":"Carlson, M. (org.Ss.eg.db: Genome wide annotation for Pig, 2019). org.Ss.eg.db: Genome wide annotation for Pig, R package Version 3.8.2."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"858","DOI":"10.3389\/fgene.2019.00858","article-title":"PathfindR: An R package for comprehensive identification of enriched pathways in omics data through active subnetworks","volume":"10","author":"Ulgen","year":"2019","journal-title":"Front. Genet."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"1830","DOI":"10.1093\/bioinformatics\/btt285","article-title":"Pathview: An R\/Bioconductor package for pathway-based data integration and visualization","volume":"29","author":"Luo","year":"2013","journal-title":"Bioinformatics"}],"container-title":["Toxins"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6651\/15\/4\/299\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:19:14Z","timestamp":1760123954000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6651\/15\/4\/299"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,19]]},"references-count":107,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2023,4]]}},"alternative-id":["toxins15040299"],"URL":"https:\/\/doi.org\/10.3390\/toxins15040299","relation":{},"ISSN":["2072-6651"],"issn-type":[{"value":"2072-6651","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4,19]]}}}