{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T05:15:23Z","timestamp":1762406123908,"version":"build-2065373602"},"reference-count":81,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T00:00:00Z","timestamp":1761782400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Human cleft lip morphopathogenesis is a complicated process involving multiple genes and proteins. Certain factors like muscle segment homeobox 1 (MSX1) and 2 (MSX2) as well as receptor-like tyrosine kinase (RYK) are important during lip embryogenesis, while others like nuclear factor kappa-B protein 65 (NF\u03baB p65), C-C motif chemokine ligand 4 (CCL4), and pentraxin 3 (PTX3) regulate local inflammation and immunomodulation. The exact role of these factors in human cleft morphopathogenesis remains uncertain and limits the opportunity to improve cleft treatment and possible prophylaxis. Immunohistochemistry (IHC) for MSX1, RYK, NF\u03baB p65, and CCL4 proteins and chromogenic in situ hybridization (CISH) for MSX2, RYK, and PTX3 genes were used to analyze postnatal human cleft lip tissue (15 patients) and control tissue (6 patients). The semiquantitative counting method was used to assess factor\/gene-signal-containing cells. Statistical analysis was performed. IHC findings showed decreased MSX1, NF\u03baB p65, and CCL4 proteins in cleft lip connective tissue and endothelium, while RYK protein was decreased only in cleft connective tissue. CISH showed increases in MSX2 and RYK gene-signal-containing cells in cleft lip tissue while PTX3 did not differ from controls. Multiple statistically significant correlations were calculated. The findings are discussed in detail to determine their significance in cleft lip morphopathogenesis.<\/jats:p>","DOI":"10.3390\/ijms262110599","type":"journal-article","created":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T01:23:59Z","timestamp":1761873839000},"page":"10599","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Analysis of MSX1, RYK, NF\u03baB p65, and CCL4 Proteins and MSX2, RYK, and PTX3 Genes in Human Cleft Lip Tissue"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8282-9733","authenticated-orcid":false,"given":"M\u0101rti\u0146\u0161","family":"Vaivads","sequence":"first","affiliation":[{"name":"Institute of Anatomy and Anthropology, R\u012bga Stradi\u0146\u0161 University, Krovalda Boulevard 9, LV-1010 Riga, Latvia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-2104-5510","authenticated-orcid":false,"given":"Alise Elizabete","family":"Rone","sequence":"additional","affiliation":[{"name":"Institute of Anatomy and Anthropology, R\u012bga Stradi\u0146\u0161 University, Krovalda Boulevard 9, LV-1010 Riga, Latvia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9804-4666","authenticated-orcid":false,"given":"M\u0101ra","family":"Pilmane","sequence":"additional","affiliation":[{"name":"Institute of Anatomy and Anthropology, R\u012bga Stradi\u0146\u0161 University, Krovalda Boulevard 9, LV-1010 Riga, Latvia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,30]]},"reference":[{"key":"ref_1","first-page":"S40","article-title":"Cleft Lip and Palate: Care Configuration, National Registration, and Research Strategies","volume":"9","author":"Sandy","year":"2020","journal-title":"J. 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