{"entity": "journal", "iuid": "6d3274beb49a4b60b727f0d2c5c7ed1f", "timestamp": "2026-07-20T00:30:52.398Z", "links": {"self": {"href": "https://publications.scilifelab.se/journal/Free%20Radic.%20Biol.%20Med..json"}, "display": {"href": "https://publications.scilifelab.se/journal/Free%20Radic.%20Biol.%20Med."}}, "title": "Free Radic. Biol. Med.", "issn": "1873-4596", "issn-l": "0891-5849", "publications_count": 5, "publications": [{"entity": "publication", "iuid": "d604787528614bb3a9cbc37e395c350b", "links": {"self": {"href": "https://publications.scilifelab.se/publication/d604787528614bb3a9cbc37e395c350b.json"}, "display": {"href": "https://publications.scilifelab.se/publication/d604787528614bb3a9cbc37e395c350b"}}, "title": "Sacrificial redox modulation by a secreted bacterial effector molecule mitigates oxidative stress and inflammation in vivo.", "authors": [{"family": "Andersson", "given": "Tilde", "initials": "T"}, {"family": "Anwaar", "given": "Shoaib", "initials": "S"}, {"family": "Fuentes-Lemus", "given": "Eduardo", "initials": "E"}, {"family": "Allhorn", "given": "Maria", "initials": "M"}, {"family": "Happonen", "given": "Lotta", "initials": "L"}, {"family": "Veitch", "given": "Margaret", "initials": "M"}, {"family": "Chew", "given": "Hui Yi", "initials": "HY"}, {"family": "Montes de Oca", "given": "Marcela", "initials": "M"}, {"family": "Tanner", "given": "Lloyd", "initials": "L"}, {"family": "Br\u00fcggemann", "given": "Holger", "initials": "H"}, {"family": "Nordenfelt", "given": "Pontus", "initials": "P"}, {"family": "Davies", "given": "Michael J", "initials": "MJ"}, {"family": "Wells", "given": "James W", "initials": "JW"}, {"family": "Lood", "given": "Rolf", "initials": "R"}], "type": "journal article", "published": "2025-12-01", "journal": {"title": "Free Radic. Biol. Med.", "issn": "1873-4596", "volume": "240", "pages": "339-346", "issn-l": "0891-5849"}, "abstract": "Human-bacterial interactions play a crucial role in several essential aspects of life. Here, we describe how a secreted protein from the skin commensal Cutibacterium acnes, RoxP, functions as a sacrificial redox effector molecule that facilitates beneficial interactions with its human host by counteracting oxidative stress and reducing stress-induced inflammation. Using a combination of structural mapping, biophysical binding studies, and in vivo experiments, we demonstrate how RoxP contributes to skin homeostasis by serving as a target for oxidative attack and influencing cytokine signaling. To our knowledge, this is the first in vivo mechanistic description of a secreted prokaryotic effector molecule modulating host redox balance through sacrificial oxidation, providing evidence of its role as a health-promoting factor.", "doi": "10.1016/j.freeradbiomed.2025.08.038", "pmid": "40849000", "labels": {"Structural Proteomics": "Collaborative"}, "xrefs": [{"db": "pii", "key": "S0891-5849(25)00925-6"}], "notes": [], "created": "2025-11-28T10:24:46.777Z", "modified": "2025-11-28T10:24:46.787Z"}, {"entity": "publication", "iuid": "e26b5b06030842c294ed6e3714352e77", "links": {"self": {"href": "https://publications.scilifelab.se/publication/e26b5b06030842c294ed6e3714352e77.json"}, "display": {"href": "https://publications.scilifelab.se/publication/e26b5b06030842c294ed6e3714352e77"}}, "title": "The acute effect of different NAD+ precursors included in the combined metabolic activators.", "authors": [{"family": "Li", "given": "Xiangyu", "initials": "X"}, {"family": "Yang", "given": "Hong", "initials": "H"}, {"family": "Jin", "given": "Han", "initials": "H"}, {"family": "Turkez", "given": "Hasan", "initials": "H"}, {"family": "Ozturk", "given": "Gurkan", "initials": "G"}, {"family": "Doganay", "given": "Hamdi Levent", "initials": "HL"}, {"family": "Zhang", "given": "Cheng", "initials": "C"}, {"family": "Nielsen", "given": "Jens", "initials": "J"}, {"family": "Uhl\u00e9n", "given": "Mathias", "initials": "M"}, {"family": "Bor\u00e9n", "given": "Jan", "initials": "J"}, {"family": "Mardinoglu", "given": "Adil", "initials": "A"}], "type": "controlled clinical trial", "published": "2023-08-20", "journal": {"title": "Free Radic. Biol. Med.", "issn": "1873-4596", "volume": "205", "pages": "77-89", "issn-l": "0891-5849"}, "abstract": "NAD+ and glutathione precursors are currently used as metabolic modulators for improving the metabolic conditions associated with various human diseases, including non-alcoholic fatty liver disease, neurodegenerative diseases, mitochondrial myopathy, and age-induced diabetes. Here, we performed a one-day double blinded, placebo-controlled human clinical study to assess the safety and acute effects of six different Combined Metabolic Activators (CMAs) with 1 g of different NAD+ precursors based on global metabolomics analysis. Our integrative analysis showed that the NAD+ salvage pathway is the main source for boosting the NAD+ levels with the administration of CMAs without NAD+ precursors. We observed that incorporation of nicotinamide (Nam) in the CMAs can boost the NAD+ products, followed by niacin (NA), nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN), but not flush free niacin (FFN). In addition, the NA administration led to a flushing reaction, accompanied by decreased phospholipids and increased bilirubin and bilirubin derivatives, which could be potentially risky. In conclusion, this study provided a plasma metabolomic landscape of different CMA formulations, and proposed that CMAs with Nam, NMN as well as NR can be administered for boosting NAD+ levels to improve altered metabolic conditions.", "doi": "10.1016/j.freeradbiomed.2023.05.032", "pmid": "37271226", "labels": {"Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "S0891-5849(23)00473-2"}], "notes": [], "created": "2023-11-27T21:44:26.698Z", "modified": "2024-01-16T13:48:32.465Z"}, {"entity": "publication", "iuid": "acab374c3a1648fcb014effd201eed3c", "links": {"self": {"href": "https://publications.scilifelab.se/publication/acab374c3a1648fcb014effd201eed3c.json"}, "display": {"href": "https://publications.scilifelab.se/publication/acab374c3a1648fcb014effd201eed3c"}}, "title": "Longitudinal metabolomics analysis reveals the acute effect of cysteine and NAC included in the combined metabolic activators.", "authors": [{"family": "Yang", "given": "Hong", "initials": "H"}, {"family": "Li", "given": "Xiangyu", "initials": "X"}, {"family": "Jin", "given": "Han", "initials": "H"}, {"family": "Turkez", "given": "Hasan", "initials": "H"}, {"family": "Ozturk", "given": "Gurkan", "initials": "G"}, {"family": "Doganay", "given": "Hamdi Levent", "initials": "HL"}, {"family": "Zhang", "given": "Cheng", "initials": "C"}, {"family": "Nielsen", "given": "Jens", "initials": "J"}, {"family": "Uhl\u00e9n", "given": "Mathias", "initials": "M"}, {"family": "Bor\u00e9n", "given": "Jan", "initials": "J"}, {"family": "Mardinoglu", "given": "Adil", "initials": "A"}], "type": "randomized controlled trial", "published": "2023-08-01", "journal": {"title": "Free Radic. Biol. Med.", "issn": "1873-4596", "volume": "204", "pages": "347-358", "issn-l": "0891-5849"}, "abstract": "Growing evidence suggests that the depletion of plasma NAD+ and glutathione (GSH) may play an important role in the development of metabolic disorders. The administration of Combined Metabolic Activators (CMA), consisting of GSH and NAD+ precursors, has been explored as a promising therapeutic strategy to target multiple altered pathways associated with the pathogenesis of the diseases. Although studies have examined the therapeutic effect of CMA that contains N-acetyl-l-cysteine (NAC) as a metabolic activator, a system-wide comparison of the metabolic response to the administration of CMA with NAC and cysteine remains lacking. In this placebo-controlled study, we studied the acute effect of the CMA administration with different metabolic activators, including NAC or cysteine with/without nicotinamide or flush free niacin, and performed longitudinal untargeted-metabolomics profiling of plasma obtained from 70 well-characterized healthy volunteers. The time-series metabolomics data revealed the metabolic pathways affected after the administration of CMAs showed high similarity between CMA containing nicotinamide and NAC or cysteine as metabolic activators. Our analysis also showed that CMA with cysteine is well-tolerated and safe in healthy individuals throughout the study. Last, our study systematically provided insights into a complex and dynamics landscape involved in amino acid, lipid and nicotinamide metabolism, reflecting the metabolic responses to CMA administration containing different metabolic activators.", "doi": "10.1016/j.freeradbiomed.2023.05.013", "pmid": "37245532", "labels": {"Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "S0891-5849(23)00429-X"}], "notes": [], "created": "2023-11-27T21:44:21.316Z", "modified": "2024-01-16T13:48:32.661Z"}, {"entity": "publication", "iuid": "170fc5031c23476881a8b932e27a23ed", "links": {"self": {"href": "https://publications.scilifelab.se/publication/170fc5031c23476881a8b932e27a23ed.json"}, "display": {"href": "https://publications.scilifelab.se/publication/170fc5031c23476881a8b932e27a23ed"}}, "title": "Serum thioredoxin reductase is highly increased in mice with hepatocellular carcinoma and its activity is restrained by several mechanisms.", "authors": [{"family": "Zhang", "given": "Le", "initials": "L"}, {"family": "Cheng", "given": "Qing", "initials": "Q"}, {"family": "Zhang", "given": "Longjie", "initials": "L"}, {"family": "Wang", "given": "Yijun", "initials": "Y"}, {"family": "Merrill", "given": "Gary F", "initials": "GF"}, {"family": "Ilani", "given": "Tal", "initials": "T"}, {"family": "Fass", "given": "Deborah", "initials": "D"}, {"family": "Arn\u00e9r", "given": "Elias S J", "initials": "ES"}, {"family": "Zhang", "given": "Jinsong", "initials": "J"}], "type": "journal article", "published": "2016-10-00", "journal": {"volume": "99", "issn": "1873-4596", "issue": null, "pages": "426-435", "title": "Free Radic. Biol. Med.", "issn-l": "0891-5849"}, "abstract": "Increased thioredoxin reductase (TrxR) levels in serum were recently identified as possible prognostic markers for human prostate cancer or hepatocellular carcinoma. We had earlier shown that serum levels of TrxR protein are very low in healthy mice, but can in close correlation to alanine aminotransferase (ALT) increase more than 200-fold upon chemically induced liver damage. We also found that enzymatic TrxR activity in serum is counteracted by a yet unidentified oxidase activity in serum. In the present study we found that mice carrying H22 hepatocellular carcinoma tumors present highly increased levels of TrxR in serum, similarly to that reported in human patients. In this case ALT levels did not parallel those of TrxR. We also discovered here that the TrxR-antagonistic oxidase activity in serum is due to the presence of quiescin Q6 sulfhydryl oxidase 1 (QSOX1). We furthermore found that the chemotherapeutic agents cisplatin or auranofin, when given systemically to H22 tumor bearing mice, can further inhibit TrxR activities in serum. The TrxR serum activity was also inhibited by endogenous electrophilic inhibitors, found to increase in tumor-bearing mice and to include protoporphyrin IX (PpIX) and 4-hydroxynonenal (HNE). Thus, hepatocellular carcinoma triggers high levels of serum TrxR that are not paralleled by ALT, and TrxR enzyme activity in serum is counteracted by several different mechanisms. The physiological role of TrxR in serum, if any, as well as its potential value as a prognostic marker for tumor progression, needs to be studied further.", "doi": "10.1016/j.freeradbiomed.2016.08.028", "pmid": "27581528", "labels": {"Mass Spectrometry-based Proteomics, Uppsala": "Service"}, "xrefs": [{"db": "pii", "key": "S0891-5849(16)30409-9"}], "notes": [], "created": "2017-05-03T13:02:35.056Z", "modified": "2017-06-12T11:40:05.532Z"}, {"entity": "publication", "iuid": "384831bd038048c29a66fa15d59e7325", "links": {"self": {"href": "https://publications.scilifelab.se/publication/384831bd038048c29a66fa15d59e7325.json"}, "display": {"href": "https://publications.scilifelab.se/publication/384831bd038048c29a66fa15d59e7325"}}, "title": "Details in the catalytic mechanism of mammalian thioredoxin reductase 1 revealed using point mutations and juglone-coupled enzyme activities.", "authors": [{"family": "Xu", "given": "Jianqiang", "initials": "J"}, {"family": "Cheng", "given": "Qing", "initials": "Q"}, {"family": "Arn\u00e9r", "given": "Elias S J", "initials": "ES"}], "type": "journal article", "published": "2016-05-00", "journal": {"volume": "94", "issn": "1873-4596", "issue": null, "pages": "110-120", "title": "Free Radic. Biol. Med.", "issn-l": "0891-5849"}, "abstract": "The mammalian selenoprotein thioredoxin reductase 1 (TrxR1) is a key enzyme in redox regulation, antioxidant defense, and cellular growth. TrxR1 can catalyze efficient reduction of juglone (5-hydroxy-1,4-naphthoquinone; walnut toxin) in a reaction which, in contrast to reduction of most other substrates of TrxR1, is not dependent upon an intact selenocysteine (Sec, U) residue of the enzyme. Using a number of TrxR1 mutant variants, we here found that a sole Cys residue at the C-terminal tail of TrxR1 is required for high-efficiency juglone-coupled NADPH oxidase activity of Sec-deficient enzyme, occurring with mixed one- and two-electron reactions producing superoxide. The activity also utilizes the FAD and the N-terminal redox active disulfide/dithiol motif of TrxR1. If a sole Cys residue at the C-terminal tail of TrxR1, in the absence of Sec, was moved further towards the C-terminal end of the protein compared to its natural position at residue 497, juglone reduction was, surprisingly, further increased. Ala substitutions of Trp407, Asn418 and Asn419 in a previously described \"guiding bar\", thought to mediate interactions of the C-terminal tail of TrxR1 with the FAD/dithiol site at the N-terminal domain of the other subunit in the dimeric enzyme, lowered turnover with juglone about 4.5-fold. Four residues of Sec-deficient TrxR1 were found to be easily arylated by juglone, including the Cys residue at position 497. Based upon our observations we suggest a model for involvement of the juglone-arylated C-terminal motif of TrxR1 to explain its high activity with juglone. This study thus provides novel insights into the catalytic mechanisms of TrxR1. One-electron juglone reduction by TrxR1 producing superoxide should furthermore contribute to the well-known prooxidant cytotoxicity of juglone.", "doi": "10.1016/j.freeradbiomed.2016.02.013", "pmid": "26898501", "labels": {"Mass Spectrometry-based Proteomics, Uppsala": "Service"}, "xrefs": [{"db": "pii", "key": "S0891-5849(16)00064-2"}], "notes": [], "created": "2017-05-03T13:02:34.764Z", "modified": "2017-06-12T11:40:05.356Z"}], "created": "2017-05-09T09:12:29.805Z", "modified": "2020-11-27T13:14:07.606Z"}