{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSERPINB1 belongs to a family of serine protease inhibitors that, much like its relative exemplified in early studies (see"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ", plays a pivotal role in restraining neutrophil‐derived proteolytic cascades. It efficiently neutralizes neutrophil serine proteases and inflammatory mediators through dual reactive motifs. In the innate immune compartment, SERPINB1 sustains neutrophil development and homeostasis"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ", limits epithelial injury in disorders such as ulcerative colitis"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ", and restricts excessive NET formation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " In addition, by binding to caspase‐recruitment domains it suppresses the activation of inflammatory caspases"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "and by forming stable complexes with cytotoxic proteases such as granzyme H"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": ", SERPINB1 helps to prevent inadvertent cell damage. Its requirement for neutrophil survival is further underscored by studies showing that deficient expression—as observed in cystic fibrosis"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": ", after conditional deletion"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": ", or in contexts of altered protease balance"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "and"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "—leads to increased neutrophil apoptosis and dysregulated cell death.\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn the oncologic setting, SERPINB1 has emerged as a negative regulator of tumor progression. Reduced expression of SERPINB1 is associated with enhanced metastatic potential in hepatocellular carcinoma"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": "and promotes migration and invasion in glioma."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": " Moreover, in cutaneous malignancies such as melanoma, higher SERPINB1 levels correlate with improved responses to cisplatin‐based chemotherapy"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "13"}]}, {"type": "t", "text": ", while its expression within the tumor microenvironment—including HPV‐associated oropharyngeal carcinomas"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "14"}]}, {"type": "t", "text": "and"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "15"}]}, {"type": "t", "text": "—is linked to more favorable outcomes. 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Its regulatory interplay with signal transducers such as STAT3 and HO‐1 may mitigate acute lung injury following liver transplantation"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "17"}]}, {"type": "t", "text": ", while proteomic studies in apical periodontitis have identified SERPINB1 as a candidate biomarker."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "18"}]}, {"type": "t", "text": " In genetic disorders like Cohen syndrome, diminished SERPINB1 expression is linked to exaggerated neutrophil apoptosis and ensuing neutropenia."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "19"}]}, {"type": "t", "text": " Furthermore, single nucleotide polymorphisms in SERPINB1 have been associated with improved β‐cell function and glycemic control in type 2 diabetes"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "20"}]}, {"type": "t", "text": ", and emerging evidence points to its involvement in acute myocardial infarction"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "21"}]}, {"type": "t", "text": "as well as in modulating trauma‐induced NETosis and adverse outcomes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "22"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "J Cooley, T K Takayama, S D Shapiro, et al. 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