{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T01:41:30Z","timestamp":1790905290318,"version":"4.1.0"},"reference-count":299,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2025,6,19]],"date-time":"2025-06-19T00:00:00Z","timestamp":1750291200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008993","name":"University of Zagreb, Zagreb, Croatia","doi-asserted-by":"publisher","award":["10106-22-3071"],"award-info":[{"award-number":["10106-22-3071"]}],"id":[{"id":"10.13039\/100008993","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Although approached through many concepts, the pleiotropic healing issue, specifically, maintaining\/reestablishing tissue integrity, remains a central challenge in pharmacology, particularly when the process is misdirected or not properly controlled. Robert and Szabo\u2019s concept of cytoprotection holds that innate cell (epithelial (Robert), endothelial (Szabo)) integrity and protection\/maintenance\/reestablishment in the stomach is translated to other organ therapy (cytoprotection \u2192 organoprotection) via the cytoprotection agent\u2019s effect. Therefore, we defend stable gastric pentadecapeptide BPC 157 therapy\u2019s efficacy and pleiotropic beneficial effects, along with its high safety (LD1 not achieved), against speculation of its negative impact, speculation of angiogenesis toward tumorigenesis, increased NO and eNOS, damaging free radical formation, and neurodegenerative diseases (Parkinson\u2019s disease and Alzheimer\u2019s disease). Contrarily, in wound healing and general healing capabilities, as reviewed, as a cytoprotective agent and native cytoprotection mediator, BPC 157 controls angiogenesis and the NO-system\u2019s healing functions and counteracts the pathological presentation of neurodegenerative diseases in acknowledged animal models (i.e., Parkinson\u2019s disease and Alzheimer\u2019s disease), and it presents prominent anti-tumor potential in vivo and in vitro. BPC 157 resolved cornea transparency maintenance, cornea healing \u201cangiogenic privilege\u201d (vs. angiogenesis\/neovascularization\/tumorigenesis), and it does not produce corneal neovascularization but rather opposes it. Per Folkman\u2019s concept, it demonstrates an anti-tumor effect in vivo and in vitro. BPC 157 exhibits a distinctive effect on the NO-level (increase vs. decrease), always combined with the counteraction of free radical formation, and, in mice and rats, BPC 157 therapy counteracts Parkinson\u2019s disease-like and Alzheimer\u2019s disease-like disturbances. Thus, BPC 157 therapy means targeting angiogenesis and NO\u2019s cytotoxic and damaging actions but maintaining, promoting, or recovering their essential protective functions.<\/jats:p>","DOI":"10.3390\/ph18060928","type":"journal-article","created":{"date-parts":[[2025,6,19]],"date-time":"2025-06-19T09:57:48Z","timestamp":1750327068000},"page":"928","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Stable Gastric Pentadecapeptide BPC 157 as a Therapy and Safety Key: A Special Beneficial Pleiotropic Effect Controlling and Modulating Angiogenesis and the NO-System"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7952-2252","authenticated-orcid":false,"given":"Predrag","family":"Sikiric","sequence":"first","affiliation":[{"name":"Department of Pharmacology, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sven","family":"Seiwerth","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9275-7283","authenticated-orcid":false,"given":"Anita","family":"Skrtic","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Staresinic","sequence":"additional","affiliation":[{"name":"Department of Surgery, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanja","family":"Strbe","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0663-3434","authenticated-orcid":false,"given":"Antonia","family":"Vuksic","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suncana","family":"Sikiric","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2941-4472","authenticated-orcid":false,"given":"Dinko","family":"Bekic","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dragan","family":"Soldo","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boris","family":"Grizelj","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luka","family":"Novosel","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia"},{"name":"Department of Diagnostic and Interventional Radiology, University Hospital Centre, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lidija","family":"Beketic Oreskovic","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivana","family":"Oreskovic","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2109-2787","authenticated-orcid":false,"given":"Mirjana","family":"Stupnisek","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alenka","family":"Boban Blagaic","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan","family":"Dobric","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia"},{"name":"Department of Surgery, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"J\u00f3zwiak, M., Bauer, M., Kamysz, W., and Kleczkowska, P. 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