{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nAlthough none of the provided abstracts explicitly mention MIR378I, the collection of studies highlights a network of innate immune responses in which antimicrobial peptides—particularly beta‐defensins—play a central role. These peptides are rapidly induced by microbial products and tissue injury via Toll‐like receptors and other pattern recognition receptors, thereby orchestrating both direct antimicrobial activity and the activation of dendritic cells to trigger adaptive responses (1."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAcross different tissue models—ranging from the skin and cornea to the intestinal, pleural, and middle ear epithelia—beta‐defensin production is tightly regulated by inflammatory mediators (e.g., IL-1β, TNF-α), intracellular receptors (e.g., NOD2), and downstream signaling cascades such as NF-κB and MAP kinases. These studies reveal that beta‐defensins not only serve as direct antimicrobial effectors but also as immunomodulators that influence cytokine profiles, immune cell recruitment, and even cell death pathways. Given the complexity of this regulation, one may hypothesize that MIR378I—if acting within the same cellular networks—could serve as a fine tuner of beta‐defensin expression or related signaling cascades."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "3", "end_ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nCollectively, these findings underscore that the regulation of innate immune effectors such as beta‐defensins is critical for host defense during infection, inflammation, and even tumor surveillance. Although the specific role of MIR378I is not defined within these reports, its potential involvement in modulating Toll-like receptor signaling, cytokine production, and cellular stress responses makes it an intriguing candidate for further research. Exploration of MIR378I’s function may reveal whether it acts upstream or in parallel to the complex regulatory circuits that ensure effective antimicrobial and immunomodulatory outcomes in diverse tissues."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "9", "end_ref": "18"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Silvia Gariboldi, Marco Palazzo, Laura Zanobbio, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Low molecular weight hyaluronic acid increases the self-defense of skin epithelium by induction of beta-defensin 2 via TLR2 and TLR4."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.181.3.2103"}], "href": "https://doi.org/10.4049/jimmunol.181.3.2103"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18641349"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18641349"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "David R Hill, Sean P Kessler, Hyunjin K Rho, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Specific-sized hyaluronan fragments promote expression of human β-defensin 2 in intestinal epithelium."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M112.356238"}], "href": "https://doi.org/10.1074/jbc.M112.356238"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22761444"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22761444"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Minhao Wu, Sharon A McClellan, Ronald P Barrett, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Beta-defensins 2 and 3 together promote resistance to Pseudomonas aeruginosa keratitis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.0902140"}], "href": "https://doi.org/10.4049/jimmunol.0902140"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19933858"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19933858"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Minhao Wu, Sharon A McClellan, Ronald P Barrett, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Beta-defensin-2 promotes resistance against infection with P. aeruginosa."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.182.3.1609"}], "href": "https://doi.org/10.4049/jimmunol.182.3.1609"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19155510"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19155510"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Arya Biragyn, Marta Coscia, Kunio Nagashima, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Murine beta-defensin 2 promotes TLR-4/MyD88-mediated and NF-kappaB-dependent atypical death of APCs via activation of TNFR2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Leukoc Biol (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1189/jlb.1007700"}], "href": "https://doi.org/10.1189/jlb.1007700"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18192488"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18192488"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Anna Manko, Jean-Paul Motta, James A Cotton, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Giardia co-infection promotes the secretion of antimicrobial peptides beta-defensin 2 and trefoil factor 3 and attenuates attaching and effacing bacteria-induced intestinal disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0178647"}], "href": "https://doi.org/10.1371/journal.pone.0178647"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28622393"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28622393"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Tajamul Hussain, Najmunnisa Nasreen, Yimu Lai, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Innate immune responses in murine pleural mesothelial cells: Toll-like receptor-2 dependent induction of beta-defensin-2 by staphylococcal peptidoglycan."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Physiol Lung Cell Mol Physiol (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/ajplung.00276.2007"}], "href": "https://doi.org/10.1152/ajplung.00276.2007"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18621910"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18621910"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Carren S Hau, Naoko Kanda, Shinji Noda, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Visfatin enhances the production of cathelicidin antimicrobial peptide, human β-defensin-2, human β-defensin-3, and S100A7 in human keratinocytes and their orthologs in murine imiquimod-induced psoriatic skin."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Pathol (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ajpath.2013.01.044"}], "href": "https://doi.org/10.1016/j.ajpath.2013.01.044"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23499548"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23499548"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Fabian Garreis, Thomas Schlorf, Dieter Worlitzsch, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Roles of human beta-defensins in innate immune defense at the ocular surface: arming and alarming corneal and conjunctival epithelial cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Histochem Cell Biol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00418-010-0713-y"}], "href": "https://doi.org/10.1007/s00418-010-0713-y"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20526610"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20526610"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Jeong-Im Woo, Sejo Oh, Paul Webster, et al. "}, {"type": "b", "children": [{"type": "t", "text": "NOD2/RICK-dependent β-defensin 2 regulation is protective for nontypeable Haemophilus influenzae-induced middle ear infection."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0090933"}], "href": "https://doi.org/10.1371/journal.pone.0090933"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24625812"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24625812"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Yoko Shibata, Shuichi Abe, Sumito Inoue, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Altered expression of antimicrobial molecules in cigarette smoke-exposed emphysematous mice lungs."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Respirology (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1440-1843.2008.01362.x"}], "href": "https://doi.org/10.1111/j.1440-1843.2008.01362.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18699806"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18699806"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Bruno Rivas-Santiago, Alberto Cervantes-Villagrana, Eduardo Sada, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Expression of beta defensin 2 in experimental pulmonary tuberculosis: tentative approach for vaccine development."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Arch Med Res (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.arcmed.2012.06.005"}], "href": "https://doi.org/10.1016/j.arcmed.2012.06.005"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22705089"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22705089"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Tamina Rückert, Geoffroy Andrieux, Melanie Boerries, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Human β-defensin 2 ameliorates acute GVHD by limiting ileal neutrophil infiltration and restraining T cell receptor signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Transl Med (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1126/scitranslmed.abp9675"}], "href": "https://doi.org/10.1126/scitranslmed.abp9675"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36542690"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36542690"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Sonam Agarwal, Anita Chauhan, Khushwant Singh, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Immunomodulatory effects of β-defensin 2 on macrophages induced immuno-upregulation and their antitumor function in breast cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "BMC Immunol (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s12865-022-00527-y"}], "href": "https://doi.org/10.1186/s12865-022-00527-y"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36324077"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36324077"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Masato Saitoh, Yoshihito Kurashige, Mami Yamazaki, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Increased expression of beta-defensin-2 and -3 during the development of autoimmune sialoadenitis in MRL/lpr mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Med Mol Morphol (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00795-007-0375-6"}], "href": "https://doi.org/10.1007/s00795-007-0375-6"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17874048"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17874048"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "E Zhuravel, T Shestakova, N Glushko, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Expression patterns of murine beta-defensin-2 mRNA in Lewis lung carcinoma cells in vitro and in vivo."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Exp Oncol (2008)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18806743"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18806743"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "Jong Kyou Kwon, Byung Hoon Chi, Se Young Choi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Murine β-defensin-2 may regulate the effect of bacillus Calmette-Guérin (BCG) in normal mouse bladder."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Urol Oncol (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.urolonc.2014.10.015"}], "href": "https://doi.org/10.1016/j.urolonc.2014.10.015"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25573055"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25573055"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "V A Chereshnev, L V Gankovskaya, L V Koval'chuk, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Expression of TLR9 and BD-2 protein genes in corneal cells of mice of different strains with herpetic keratitis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Bull Exp Biol Med (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s10517-012-1685-9"}], "href": "https://doi.org/10.1007/s10517-012-1685-9"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22816092"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22816092"}]}]}]}