{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T22:53:56Z","timestamp":1791500036941,"version":"4.3.4"},"reference-count":67,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2023,8,30]],"date-time":"2023-08-30T00:00:00Z","timestamp":1693353600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002081","name":"Irish Research Council","doi-asserted-by":"publisher","award":["GOIPD\/2020\/336"],"award-info":[{"award-number":["GOIPD\/2020\/336"]}],"id":[{"id":"10.13039\/501100002081","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000296","name":"British Skin Foundation","doi-asserted-by":"publisher","award":["010\/BSFSG\/21"],"award-info":[{"award-number":["010\/BSFSG\/21"]}],"id":[{"id":"10.13039\/501100000296","id-type":"DOI","asserted-by":"publisher"}]},{"name":"City of Dublin Skin and Cancer Hospital Charity"},{"name":"Irish Clinical Academic 6 Training Programme"},{"name":"Wellcome Trust and the Health Research Board","award":["203930\/B\/16\/Z"],"award-info":[{"award-number":["203930\/B\/16\/Z"]}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,11,16]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Targeting immunometabolism has shown promise in treating autoimmune and inflammatory conditions. Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease involving painful lesions in apocrine gland-bearing skin. Therapeutic options for HS are limited and often ineffective; thus, there is a pressing need for improved treatments. To date, metabolic dysregulation has not been investigated in HS. As HS is highly inflammatory, we hypothesized that energy metabolism is dysregulated in these patients. Metformin, an antidiabetic drug, which is known to impact on cellular metabolic and signalling pathways, has been shown to have anti-inflammatory effects in cancer and arthritis. While metformin is not licensed for use in HS, patients with HS taking metformin show improved clinical symptoms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To assess the effect and mechanism of action of metformin in HS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>To assess the effect of metformin in vivo, we compared the immune and metabolic profiles of peripheral blood mononuclear cells (PBMCs) of patients with HS taking metformin vs. those not taking metformin. To examine the effect of metformin treatment ex vivo, we employed a skin explant model on skin biopsies from patients with HS not taking metformin, which we cultured with metformin overnight. We used enzyme-linked immunosorbent assays, multiplex cytokine assays and quantitative real-time polymerase chain reaction (RT-PCR) to measure inflammatory markers, and Seahorse flux technology and quantitative RT-PCR to assess glucose metabolism.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We showed that metabolic pathways are dysregulated in the PBMCs of patients with HS vs. healthy individuals. In metformin-treated patients, these metabolic pathways were restored and their PBMCs had reduced inflammatory markers following long-term metformin treatment. In the skin explant model, we found that overnight culture with metformin reduced inflammatory cytokines and chemokines and glycolytic genes in lesions and tracts of patients with HS. Using in vitro assays, we found that metformin may induce these changes via the NLR family pyrin domain containing 3 (NLRP3) inflammasome and the AMP-activated protein kinase (AMPK)\u2013mammalian target of rapamycin (mTOR) pathway, which is linked to glycolysis and protein synthesis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our study provides insight into the mechanisms of action of metformin in HS. The anti-inflammatory effects of metformin support its use as a therapeutic agent in HS, while its effects on immunometabolism suggest that targeting metabolism is a promising therapeutic option in inflammatory diseases, including HS.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/bjd\/ljad305","type":"journal-article","created":{"date-parts":[[2023,8,28]],"date-time":"2023-08-28T08:52:11Z","timestamp":1693212731000},"page":"730-740","source":"Crossref","is-referenced-by-count":50,"title":["Metformin has anti-inflammatory effects and induces immunometabolic reprogramming via multiple mechanisms in hidradenitis suppurativa"],"prefix":"10.1093","volume":"189","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0420-5252","authenticated-orcid":false,"given":"Andreea","family":"Petrasca","sequence":"first","affiliation":[{"name":"School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin , Dublin ,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7050-738X","authenticated-orcid":false,"given":"Roisin","family":"Hambly","sequence":"additional","affiliation":[{"name":"Department of Dermatology, St. Vincent\u2019s University Hospital , Dublin ,","place":["Ireland"]},{"name":"Charles Institute of Dermatology , Dublin ,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6469-3462","authenticated-orcid":false,"given":"Niamh","family":"Kearney","sequence":"additional","affiliation":[{"name":"Department of Dermatology, St. Vincent\u2019s University Hospital , Dublin ,","place":["Ireland"]},{"name":"Charles Institute of Dermatology , Dublin ,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1701-1665","authenticated-orcid":false,"given":"Conor M","family":"Smith","sequence":"additional","affiliation":[{"name":"School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin , Dublin ,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1763-3173","authenticated-orcid":false,"given":"Emily\u00a0K","family":"Pender","sequence":"additional","affiliation":[{"name":"Department of Dermatology, St. Vincent\u2019s University Hospital , Dublin ,","place":["Ireland"]},{"name":"Charles Institute of Dermatology , Dublin ,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4239-3215","authenticated-orcid":false,"given":"Julie","family":"Mac Mahon","sequence":"additional","affiliation":[{"name":"Department of Dermatology, St. Vincent\u2019s University Hospital , Dublin ,","place":["Ireland"]},{"name":"Charles Institute of Dermatology , Dublin ,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9882-2907","authenticated-orcid":false,"given":"Aoife M","family":"O\u2019Rourke","sequence":"additional","affiliation":[{"name":"School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin , Dublin ,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5840-5137","authenticated-orcid":false,"given":"Mohamed","family":"Ismaiel","sequence":"additional","affiliation":[{"name":"Department of Surgery, St. Michael\u2019s Hospital , Dublin ,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5844-7695","authenticated-orcid":false,"given":"Patrick A","family":"Boland","sequence":"additional","affiliation":[{"name":"Department of Surgery, St. Michael\u2019s Hospital , Dublin ,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-2323-3572","authenticated-orcid":false,"given":"Jose P","family":"Almeida","sequence":"additional","affiliation":[{"name":"Department of Surgery, St. Michael\u2019s Hospital , Dublin ,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8983-7231","authenticated-orcid":false,"given":"Czara","family":"Kennedy","sequence":"additional","affiliation":[{"name":"Department of Surgery, St. Michael\u2019s Hospital , Dublin ,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0894-4079","authenticated-orcid":false,"given":"Alexandra","family":"Zaborowski","sequence":"additional","affiliation":[{"name":"Department of Surgery, St. Michael\u2019s Hospital , Dublin ,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siun","family":"Murphy","sequence":"additional","affiliation":[{"name":"Department of Plastic Reconstructive and Aesthetic Surgery, Blackrock Clinic , Dublin ,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9559-6438","authenticated-orcid":false,"given":"Desmond","family":"Winter","sequence":"additional","affiliation":[{"name":"Department of Surgery, St. Michael\u2019s Hospital , Dublin ,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7596-892X","authenticated-orcid":false,"given":"Brian","family":"Kirby","sequence":"additional","affiliation":[{"name":"Department of Dermatology, St. Vincent\u2019s University Hospital , Dublin ,","place":["Ireland"]},{"name":"Charles Institute of Dermatology , Dublin ,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0670-6659","authenticated-orcid":false,"given":"Jean M","family":"Fletcher","sequence":"additional","affiliation":[{"name":"School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin , Dublin ,","place":["Ireland"]},{"name":"School of Medicine, Trinity Biomedical Sciences Institute, Trinity College Dublin , Dublin ,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,8,30]]},"reference":[{"key":"2026041404170107300_ljad305-B1","doi-asserted-by":"crossref","first-page":"2094","DOI":"10.3390\/cells10082094","article-title":"Hidradenitis suppurativa: where we are and where we are going","volume":"10","author":"Scala","year":"2021","journal-title":"Cells"},{"key":"2026041404170107300_ljad305-B2","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1016\/j.ijwd.2019.06.026","article-title":"Comorbidities of hidradenitis suppurativa: a review of the literature","volume":"5","author":"Cartron","year":"2019","journal-title":"Int J Womens Dermatol"},{"key":"2026041404170107300_ljad305-B3","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1016\/j.jaad.2019.08.090","article-title":"Hidradenitis suppurativa: epidemiology, clinical presentation, and pathogenesis","volume":"82","author":"Goldburg","year":"2020","journal-title":"J Am Acad Dermatol"},{"key":"2026041404170107300_ljad305-B4","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1038\/s41572-020-0149-1","article-title":"Hidradenitis suppurativa","volume":"6","author":"Sabat","year":"2020","journal-title":"Nat Rev Dis Primers"},{"key":"2026041404170107300_ljad305-B5","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1016\/j.jaad.2019.08.089","article-title":"Hidradenitis suppurativa: current and emerging treatments","volume":"82","author":"Goldburg","year":"2020","journal-title":"J Am Acad Dermatol"},{"key":"2026041404170107300_ljad305-B6","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1056\/NEJMoa1504370","article-title":"Two phase 3 trials of adalimumab for hidradenitis suppurativa","volume":"375","author":"Kimball","year":"2016","journal-title":"N Engl J Med"},{"key":"2026041404170107300_ljad305-B7","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1111\/cei.13228","article-title":"Altered metabolic pathways regulate synovial inflammation in rheumatoid arthritis","volume":"197","author":"Fearon","year":"2019","journal-title":"Clin Exp Immunol"},{"key":"2026041404170107300_ljad305-B8","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/bs.acr.2019.03.004","article-title":"Immunometabolism: a new target for improving cancer immunotherapy","volume":"143","author":"Guo","year":"2019","journal-title":"Adv Cancer Res"},{"key":"2026041404170107300_ljad305-B9","doi-asserted-by":"crossref","first-page":"e1486","DOI":"10.1002\/wsbm.1486","article-title":"The immunologic Warburg effect: evidence and therapeutic opportunities in autoimmunity","volume":"12","author":"Kornberg","year":"2020","journal-title":"Wiley Interdiscip Rev Syst Biol Med"},{"key":"2026041404170107300_ljad305-B10","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1038\/s41422-020-0291-z","article-title":"Targeting immunometabolism as an anti-inflammatory strategy","volume":"30","author":"P\u00e5lsson-Mcdermott","year":"2020","journal-title":"Cell Res"},{"key":"2026041404170107300_ljad305-B11","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.intimp.2019.05.002","article-title":"Inflammation research sails through the sea of immunology to reach immunometabolism","volume":"73","author":"Kumar","year":"2019","journal-title":"Int Immunopharmacol"},{"key":"2026041404170107300_ljad305-B12","doi-asserted-by":"crossref","first-page":"155223","DOI":"10.1016\/j.metabol.2022.155223","article-title":"Metformin: Is it a drug for all reasons and diseases?","volume":"133","author":"Triggle","year":"2022","journal-title":"Metabolism"},{"key":"2026041404170107300_ljad305-B13","doi-asserted-by":"crossref","first-page":"C873","DOI":"10.1152\/ajpcell.00604.2020","article-title":"The intersection of metformin and inflammation","volume":"320","author":"Bharath","year":"2021","journal-title":"Am J Physiol Cell Physiol"},{"key":"2026041404170107300_ljad305-B14","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1080\/09546634.2019.1592100","article-title":"Metformin use in hidradenitis suppurativa","volume":"31","author":"Jennings","year":"2020","journal-title":"J Dermatolog Treat"},{"key":"2026041404170107300_ljad305-B15","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1111\/j.1468-3083.2012.04668.x","article-title":"Metformin for the treatment of hidradenitis suppurativa: a little help along the way","volume":"27","author":"Verdolini","year":"2013","journal-title":"J Eur Acad Dermatol Venereol"},{"key":"2026041404170107300_ljad305-B16","doi-asserted-by":"crossref","first-page":"1010","DOI":"10.7150\/ijbs.29680","article-title":"Metformin inhibits the NLRP3 inflammasome via AMPK\/mTOR-dependent effects in diabetic cardiomyopathy","volume":"15","author":"Yang","year":"2019","journal-title":"Int J Biol Sci"},{"key":"2026041404170107300_ljad305-B17","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1146\/annurev-med-062613-093128","article-title":"Metformin in cancer treatment and prevention","volume":"66","author":"Morales","year":"2015","journal-title":"Annu Rev Med"},{"key":"2026041404170107300_ljad305-B18","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1038\/nrm.2017.95","article-title":"AMPK: guardian of metabolism and mitochondrial homeostasis","volume":"19","author":"Herzig","year":"2018","journal-title":"Nat Rev Mol Cell Biol"},{"key":"2026041404170107300_ljad305-B19","doi-asserted-by":"crossref","first-page":"2816","DOI":"10.1093\/rheumatology\/kez682","article-title":"Targeting bioenergetics prevents CD4 T cell-mediated activation of synovial fibroblasts in rheumatoid arthritis","volume":"59","author":"Petrasca","year":"2020","journal-title":"Rheumatology (Oxford"},{"key":"2026041404170107300_ljad305-B20","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1002\/art.41190","article-title":"Insulin-resistant pathways are associated with disease activity in rheumatoid arthritis and are subject to disease modification through metabolic reprogramming: a potential novel therapeutic approach","volume":"72","author":"Gallagher","year":"2020","journal-title":"Arthritis Rheumatol"},{"key":"2026041404170107300_ljad305-B21","doi-asserted-by":"crossref","first-page":"726490","DOI":"10.3389\/fphar.2021.726490","article-title":"Efficacy and safety of metformin use in rheumatoid arthritis: a randomized controlled study","volume":"12","author":"Gharib","year":"2021","journal-title":"Front Pharmacol"},{"key":"2026041404170107300_ljad305-B22","doi-asserted-by":"crossref","first-page":"820","DOI":"10.1111\/jdv.14894","article-title":"Insulin resistance in hidradenitis suppurativa: a case\u2013control study","volume":"32","author":"Vilanova","year":"2018","journal-title":"J Eur Acad Dermatol Venereol"},{"key":"2026041404170107300_ljad305-B23","first-page":"56","article-title":"Metformin use in women with polycystic ovary syndrome","volume":"2","author":"Johnson","year":"2014","journal-title":"Ann Transl Med"},{"key":"2026041404170107300_ljad305-B24","doi-asserted-by":"crossref","first-page":"e12953","DOI":"10.1111\/dth.12953","article-title":"Metformin as an adjunct therapy for the treatment of moderate to severe acne vulgaris: a randomized open-labeled study","volume":"32","author":"Robinson","year":"2019","journal-title":"Dermatol Ther"},{"key":"2026041404170107300_ljad305-B25","doi-asserted-by":"crossref","DOI":"10.5070\/D32311037242","article-title":"Metformin as an adjunct therapy for the treatment of moderate to severe acne vulgaris","volume":"23","author":"Lee","year":"2017","journal-title":"Dermatol Online J"},{"key":"2026041404170107300_ljad305-B26","doi-asserted-by":"crossref","first-page":"966","DOI":"10.1111\/exd.14347","article-title":"Effects of metformin on experimentally induced acne on rabbit ear","volume":"30","author":"Kamboj","year":"2021","journal-title":"Exp Dermatol"},{"key":"2026041404170107300_ljad305-B27","doi-asserted-by":"crossref","first-page":"6969","DOI":"10.3390\/ijms24086969","article-title":"Metformin treatment of hidradenitis suppurativa: effect on metabolic parameters, inflammation, cardiovascular risk biomarkers, and immune mediators","volume":"24","author":"Hambly","year":"2023","journal-title":"Int J Mol Sci"},{"key":"2026041404170107300_ljad305-B28","doi-asserted-by":"crossref","first-page":"2107","DOI":"10.1007\/s00403-023-02594-6","article-title":"Overexpression of hypoxia-inducible factor-1\u03b1 in hidradenitis suppurativa: the link between deviated immunity and metabolism","volume":"315","author":"Agamia","year":"2023","journal-title":"Arch Dermatol Res"},{"key":"2026041404170107300_ljad305-B29","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1016\/j.cell.2017.04.004","article-title":"Metabolic instruction of immunity","volume":"169","author":"Buck","year":"2017","journal-title":"Cell"},{"key":"2026041404170107300_ljad305-B30","doi-asserted-by":"crossref","first-page":"53562","DOI":"10.1074\/jbc.M406096200","article-title":"6-Phosphofructo-2-kinase (pfkfb3) gene promoter contains hypoxia-inducible factor-1 binding sites necessary for transactivation in response to hypoxia","volume":"279","author":"Obach","year":"2004","journal-title":"J Biol Chem"},{"key":"2026041404170107300_ljad305-B31","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1101\/gad.1529107","article-title":"The transcription factor HIF-1\u03b1 plays a critical role in the growth factor-dependent regulation of both aerobic and anaerobic glycolysis","volume":"21","author":"Lum","year":"2007","journal-title":"Genes Dev"},{"key":"2026041404170107300_ljad305-B32","doi-asserted-by":"crossref","first-page":"2445","DOI":"10.1038\/sj.jid.5700874","article-title":"Upregulation of hypoxia-inducible factors in normal and psoriatic skin","volume":"127","author":"Rosenberger","year":"2007","journal-title":"J Invest Dermatol"},{"key":"2026041404170107300_ljad305-B33","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.cyto.2013.02.029","article-title":"High serum levels of HIF-1\u03b1 in psoriatic patients correlate with an over-expression of IL-6","volume":"62","author":"Vasilopoulos","year":"2013","journal-title":"Cytokine"},{"key":"2026041404170107300_ljad305-B34","doi-asserted-by":"crossref","first-page":"R461","DOI":"10.1530\/ERC-14-0284","article-title":"Metformin, cancer and glucose metabolism","volume":"21","author":"Salani","year":"2014","journal-title":"Endocr Relat Cancer"},{"key":"2026041404170107300_ljad305-B35","doi-asserted-by":"crossref","first-page":"2482","DOI":"10.1158\/1078-0432.CCR-17-3070","article-title":"Oxidative phosphorylation as an emerging target in cancer therapy","volume":"24","author":"Ashton","year":"2018","journal-title":"Clin Cancer Res"},{"key":"2026041404170107300_ljad305-B36","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1038\/s41422-020-0301-1","article-title":"Signaling networks in immunometabolism","volume":"30","author":"Saravia","year":"2020","journal-title":"Cell Res"},{"key":"2026041404170107300_ljad305-B37","doi-asserted-by":"crossref","first-page":"1441","DOI":"10.1016\/j.jaad.2020.06.042","article-title":"Sirolimus as combination rescue therapy with tumor necrosis alpha inhibitors for severe, refractory hidradenitis suppurativa","volume":"83","author":"Bettuzzi","year":"2020","journal-title":"J Am Acad Dermatol"},{"key":"2026041404170107300_ljad305-B38","doi-asserted-by":"crossref","first-page":"1631","DOI":"10.1111\/jdv.13233","article-title":"Mammalian target of rapamycin, insulin resistance and hidradenitis suppurativa: a possible metabolic loop","volume":"30","author":"Monfrecola","year":"2016","journal-title":"J Eur Acad Dermatol Venereol"},{"key":"2026041404170107300_ljad305-B39","doi-asserted-by":"crossref","first-page":"e444","DOI":"10.1111\/jdv.17202","article-title":"mTORC1 \u2013 a potential player in the pathogenesis of hidradenitis suppurativa?","volume":"35","author":"Dmitriev","year":"2021","journal-title":"J Eur Acad Dermatol Venereol"},{"key":"2026041404170107300_ljad305-B40","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1002\/eji.201545886","article-title":"mTORC1 signaling and IL-17 expression: defining pathways and possible therapeutic targets","volume":"46","author":"Ren","year":"2016","journal-title":"Eur J Immunol"},{"key":"2026041404170107300_ljad305-B41","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1111\/nyas.12059","article-title":"Role of PI3K\/Akt and mTOR complexes in Th17 cell differentiation","author":"Nagai","year":"2013","journal-title":"Ann N Y Acad Sci"},{"key":"2026041404170107300_ljad305-B42","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1111\/cei.13449","article-title":"IL-17 in inflammatory skin diseases psoriasis and hidradenitis suppurativa","volume":"201","author":"Fletcher","year":"2020","journal-title":"Clin Exp Immunol"},{"key":"2026041404170107300_ljad305-B43","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1038\/nrd3794","article-title":"Targeting IL-17 and TH17 cells in chronic inflammation","volume":"11","author":"Miossec","year":"2012","journal-title":"Nat Rev Drug Discov"},{"key":"2026041404170107300_ljad305-B44","doi-asserted-by":"crossref","first-page":"50","DOI":"10.25122\/jml-2020-0029","article-title":"The influence of metformin to the transcriptional activity of the mTOR and FOX3 genes in parapancreatic adipose tissue of streptozotocin-induced diabetic rats","volume":"13","author":"Putilin","year":"2020","journal-title":"J Med Life"},{"key":"2026041404170107300_ljad305-B45","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.3109\/13880209.2015.1057652","article-title":"Metformin inhibits proliferation and proinflammatory cytokines of human keratinocytes in vitro via mTOR-signaling pathway","volume":"54","author":"Liu","year":"2016","journal-title":"Pharm Biol"},{"key":"2026041404170107300_ljad305-B46","doi-asserted-by":"crossref","DOI":"10.3390\/ijms20133328","article-title":"The NLRP3 inflammasome: an overview of mechanisms of activation and regulation","volume":"20","author":"Kelley","year":"2019","journal-title":"Int J Mol Sci"},{"key":"2026041404170107300_ljad305-B47","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1093\/bjd\/ljad184","article-title":"Targeting the NLRP3 inflammasome reduces inflammation in hidradenitis suppurativa skin","volume":"189","author":"Moran","year":"2023","journal-title":"Br J Dermatol"},{"key":"2026041404170107300_ljad305-B48","doi-asserted-by":"crossref","first-page":"1294","DOI":"10.1016\/j.jid.2018.11.018","article-title":"The IL-1 pathway is hyperactive in hidradenitis suppurativa and contributes to skin infiltration and destruction","volume":"139","author":"Witte-H\u00e4ndel","year":"2019","journal-title":"J Invest Dermatol"},{"key":"2026041404170107300_ljad305-B49","doi-asserted-by":"crossref","first-page":"1463","DOI":"10.1016\/j.immuni.2021.05.004","article-title":"Metformin inhibition of mitochondrial ATP and DNA synthesis abrogates NLRP3 inflammasome activation and pulmonary inflammation","volume":"54","author":"Xian","year":"2021","journal-title":"Immunity"},{"key":"2026041404170107300_ljad305-B50","doi-asserted-by":"crossref","first-page":"24270","DOI":"10.18632\/aging.202143","article-title":"Metformin protects against myocardial ischemia-reperfusion injury and cell pyroptosis via AMPK\/NLRP3 inflammasome pathway","volume":"12","author":"Zhang","year":"2020","journal-title":"Aging"},{"key":"2026041404170107300_ljad305-B51","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1038\/s41420-020-0245-8","article-title":"Metformin inhibits IL-1\u03b2 secretion via impairment of NLRP3 inflammasome in keratinocytes: implications for preventing the development of psoriasis","volume":"6","author":"Tsuji","year":"2020","journal-title":"Cell Death Discov"},{"key":"2026041404170107300_ljad305-B52","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1016\/j.intimp.2016.09.024","article-title":"The neuroprotection of Sinomenine against ischemic stroke in mice by suppressing NLRP3 inflammasome via AMPK signaling","volume":"40","author":"Qiu","year":"2016","journal-title":"Int Immunopharmacol"},{"key":"2026041404170107300_ljad305-B53","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1089\/ars.2014.6120","article-title":"AMPK phosphorylation modulates pain by activation of NLRP3 inflammasome","volume":"24","author":"Bull\u00f3n","year":"2016","journal-title":"Antioxid Redox Signal"},{"key":"2026041404170107300_ljad305-B54","article-title":"Metformin: an inhibitor of mTORC1 signaling","volume":"2","author":"Melnik","year":"2014","journal-title":"J Endocrinol Diabetes Obes"},{"key":"2026041404170107300_ljad305-B55","doi-asserted-by":"crossref","first-page":"2245","DOI":"10.18632\/aging.101319","article-title":"Towards natural mimetics of metformin and rapamycin","volume":"9","author":"Aliper","year":"2017","journal-title":"Aging"},{"key":"2026041404170107300_ljad305-B56","doi-asserted-by":"crossref","first-page":"1475","DOI":"10.1038\/onc.2012.181","article-title":"Targeting metabolism for cancer treatment and prevention: metformin, an old drug with multi-faceted effects","volume":"32","author":"Pierotti","year":"2013","journal-title":"Oncogene"},{"key":"2026041404170107300_ljad305-B57","doi-asserted-by":"crossref","first-page":"204","DOI":"10.3892\/ol.2022.13325","article-title":"Metformin: a promising drug for human cancers","volume":"24","author":"Wu","year":"2022","journal-title":"Oncol Lett"},{"key":"2026041404170107300_ljad305-B58","first-page":"1713","article-title":"Regulation of mTORC1 and its impact on gene expression at a glance","volume":"126","author":"Laplante","year":"2013","journal-title":"J Cell Sci"},{"key":"2026041404170107300_ljad305-B59","doi-asserted-by":"crossref","first-page":"1250684","DOI":"10.1126\/science.1250684","article-title":"mTOR- and HIF-1\u03b1-mediated aerobic glycolysis as metabolic basis for trained immunity","volume":"345","author":"Cheng","year":"2014","journal-title":"Science"},{"key":"2026041404170107300_ljad305-B60","doi-asserted-by":"crossref","first-page":"109770","DOI":"10.1016\/j.intimp.2023.109770","article-title":"STAT3 as a therapeutic target in the metformin-related treatment","volume":"116","author":"Zhang","year":"2023","journal-title":"Int Immunopharmacol"},{"key":"2026041404170107300_ljad305-B61","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1186\/s12967-021-02860-z","article-title":"Metformin ameliorates scleroderma via inhibiting Th17 cells and reducing mTOR-STAT3 sig\u00adnaling in skin fibroblasts","volume":"19","author":"Moon","year":"2021","journal-title":"J Transl Med"},{"key":"2026041404170107300_ljad305-B62","doi-asserted-by":"crossref","first-page":"2389","DOI":"10.1016\/j.jid.2017.05.033","article-title":"Hidradenitis suppurativa is characterized by dysregulation of the Th17:Treg cell axis, which is corrected by anti-TNF therapy","volume":"137","author":"Moran","year":"2017","journal-title":"J Invest Dermatol"},{"key":"2026041404170107300_ljad305-B63","first-page":"260","article-title":"T helper 17 cell\/\u00adregulatory\u00a0T-cell imbalance in hidradenitis suppurativa\/acne\u00a0inversa: the link to hair follicle dissection, obesity, smoking\u00a0and autoimmune comorbidities","volume":"179","author":"Melnik","year":"2018","journal-title":"Br J Dermatol"},{"key":"2026041404170107300_ljad305-B64","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.1084\/jem.20110278","article-title":"HIF1\u03b1-dependent glycolytic pathway orchestrates a metabolic checkpoint for the differentiation of TH17 and Treg cells","volume":"208","author":"Shi","year":"2011","journal-title":"J Exp Med"},{"key":"2026041404170107300_ljad305-B65","doi-asserted-by":"crossref","first-page":"3699","DOI":"10.1172\/JCI84431","article-title":"HIF1\u03b1 and metabolic reprogramming in inflammation","volume":"126","author":"Corcoran","year":"2016","journal-title":"J Clin Invest"},{"key":"2026041404170107300_ljad305-B66","doi-asserted-by":"crossref","first-page":"1339","DOI":"10.1016\/j.cell.2014.05.012","article-title":"Increased adipocyte O2 consumption triggers HIF-1\u03b1, causing inflammation and insulin resistance in obesity","volume":"157","author":"Lee","year":"2014","journal-title":"Cell"},{"key":"2026041404170107300_ljad305-B67","doi-asserted-by":"crossref","first-page":"e107","DOI":"10.1111\/jdv.15270","article-title":"mTORC1 at the crossroad of metabolism and immunity in hidradenitis suppurativa","volume":"33","author":"De Vita","year":"2019","journal-title":"J Eur Acad Dermatol Venereol"}],"container-title":["British Journal of Dermatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bjd\/advance-article-pdf\/doi\/10.1093\/bjd\/ljad305\/51717130\/ljad305.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bjd\/article-pdf\/189\/6\/730\/58992319\/ljad305.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bjd\/article-pdf\/189\/6\/730\/58992319\/ljad305.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T08:17:23Z","timestamp":1776154643000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bjd\/article\/189\/6\/730\/7256193"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8,30]]},"references-count":67,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2023,8,30]]},"published-print":{"date-parts":[[2023,11,16]]}},"URL":"https:\/\/doi.org\/10.1093\/bjd\/ljad305","relation":{},"ISSN":["0007-0963","1365-2133"],"issn-type":[{"value":"0007-0963","type":"print"},{"value":"1365-2133","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2023,12]]},"published":{"date-parts":[[2023,8,30]]}}}