{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T07:10:24Z","timestamp":1792480224138,"version":"4.5.0"},"reference-count":23,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2022,12,16]],"date-time":"2022-12-16T00:00:00Z","timestamp":1671148800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100014438","name":"Business Finland","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100014438","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Health Science Reports"],"published-print":{"date-parts":[[2023,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background and Aims<\/jats:title><jats:p>Natural coniferous resins are used in traditional medicine for the treatment of skin wounds. Coniferous wood resins (\u201ccallus\u201d resin) are a mixture of abietic (resin) acids, lignans such as pinoresinol, and <jats:italic>p<\/jats:italic>\u2010coumaric acid. The wound\u2010healing properties of resins are thought to be related to their antimicrobial properties, but also to their effects on cell proliferation and inflammation. The purpose of this study was to identify and investigate the effects of novel aqueous dispersions of resin and its main components in the proliferation of human primary keratinocytes in vitro\u00a0and in the expression of proinflammatory cytokines in human peripheral blood mononuclear cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The proliferation studies were performed under low and high calcium conditions with or without added growth stimulators at the time points of 2\u00a0and 6 days using AlamarBlue Cell Viability Reagent. The cytokine release assay was carried out by incubating the cells with the test articles for 18\u2009h, after which the levels of tumor necrosis factor\u2010\u03b1\u00a0(TNF\u2010\u03b1),\u00a0interleukin\u20101\u03b2 (IL\u20101\u03b2), IL\u20106, and IL\u20108 were measured in the supernatant by enzyme\u2010linked immunosorbent assay.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Resin and the purified lignan PINO, but not <jats:italic>p<\/jats:italic>\u2010coumaric acid or abietic acid (industrial tall oil rosin), enhanced the proliferation of human keratinocytes in vitro\u00a0and inhibited the expression of TNF\u2010\u03b1, and to a lesser extent the expression of IL\u20101\u03b2 in peripheral blood mononuclear cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>In this study, novel aqueous dispersions of spruce resin were used to investigate the effects of main resin components on keratinocyte proliferation and on the expression of key proinflammatory cytokines known to be associated with chronic wounds. The observations suggest that lignans, such as PINO, but not resin acids, are the components of resins that mediate the proliferative and TNF\u2010\u03b1\u2010suppressing effects. Lignans including PINO were identified as novel potential compounds in the treatment of chronic skin ulcers.<\/jats:p><\/jats:sec>","DOI":"10.1002\/hsr2.998","type":"journal-article","created":{"date-parts":[[2022,12,17]],"date-time":"2022-12-17T06:49:00Z","timestamp":1671259740000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Pinoresinol stimulates keratinocyte proliferation and downregulates TNF\u2010\u03b1 secretion in peripheral blood mononuclear cells: An experimental in vitro study"],"prefix":"10.1002","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2098-3596","authenticated-orcid":false,"given":"Elias","family":"Haapakorva","sequence":"first","affiliation":[{"name":"Kasve Ltd Kuopio Finland"},{"name":"School of Pharmacy University of Eastern Finland  Kuopio Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannu","family":"Raunio","sequence":"additional","affiliation":[{"name":"School of Pharmacy University of Eastern Finland  Kuopio Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atte","family":"von Wright","sequence":"additional","affiliation":[{"name":"Institute of Public Health and Clinical Nutrition University of Eastern Finland  Kuopio Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilkka","family":"Harvima","sequence":"additional","affiliation":[{"name":"Department of Dermatology University of Eastern Finland and Kuopio University Hospital  Kuopio Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,12,16]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1055\/a-1141-0921"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/jam.13640"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0463.2011.02791.x"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0463.2007.apm_548.x"},{"key":"e_1_2_12_6_1","article-title":"Peripheral rearterialization for critical limb ischaemia and antiseptic resin or honey salve in postoperative ulcer care results in healing rate of leg ulcers in three quarters of cases. A prospective clinical follow\u2010up of 35 patients with preoperative chronic ulcer and 5 patients with post\u2010surgery wound surgical site infection","volume":"5","author":"Auvinen T","year":"2020","journal-title":"J Surg"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2133.2008.08461.x"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1089\/wound.2013.0492"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0043-1354(99)00406-6"},{"issue":"3","key":"e_1_2_12_10_1","first-page":"2143","article-title":"Pinoresinol promotes MC3T3\u2010E1 cell proliferation and differentiation via the cyclic AMP\/protein kinase\u2014a signaling pathway","volume":"20","author":"Jiang X","year":"2019","journal-title":"Mol Med Rep"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1023\/B:PHYT.0000045493.95074.a8"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-0625.2001.010003184.x"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1080\/000155599750011011"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra050541"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1586\/1744666X.2014.894886"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.69.4.513"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V74.1.1.1"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines8050101"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0086147"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1524-475X.2008.00410.x"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdermsci.2019.11.004"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1524-475X.1996.40404.x"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2020.4006"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules26164917"}],"container-title":["Health Science Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/hsr2.998","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/hsr2.998","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/hsr2.998","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,24]],"date-time":"2023-08-24T07:24:04Z","timestamp":1692861844000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/hsr2.998"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,16]]},"references-count":23,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2023,1]]}},"alternative-id":["10.1002\/hsr2.998"],"URL":"https:\/\/doi.org\/10.1002\/hsr2.998","archive":["Portico"],"relation":{},"ISSN":["2398-8835","2398-8835"],"issn-type":[{"value":"2398-8835","type":"print"},{"value":"2398-8835","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,16]]},"assertion":[{"value":"2022-08-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-12-05","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-12-16","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e998"}}