{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T14:02:36Z","timestamp":1785420156023,"version":"3.56.0"},"reference-count":29,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T00:00:00Z","timestamp":1776988800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002383","name":"King Saud University","doi-asserted-by":"crossref","award":["ORF-2026-1219"],"award-info":[{"award-number":["ORF-2026-1219"]}],"id":[{"id":"10.13039\/501100002383","id-type":"DOI","asserted-by":"crossref"}]},{"award":["ORF-2026-1219"],"award-info":[{"award-number":["ORF-2026-1219"]}],"id":[{"id":"https:\/\/ror.org\/02f81g417","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["ARM"],"abstract":"<jats:p>Background: Surfactant Protein D (SP-D) is a critical immunomodulatory collectin maintaining alveolar homeostasis. Obstructive sleep apnea (OSA)-related intermittent hypoxia (IH) disrupts pulmonary surfactant integrity; however, severity-dependent SP-D dynamics remain incompletely characterized. This study explores SP-D as a potential indicator of IH-induced alveolar stress and evaluates whether Galectin-3 (Gal-3) inhibition modulates surfactant homeostasis. Methods: Forty adult male Sprague-Dawley rats (8 per group) were randomized to Control (normoxia), Moderate IH (MIH; 15\u201330 events\/hour), Severe IH (SIH; 30\u201360 events\/hour), MIH + Gal-3 inhibitor (Modified Citrus Pectin, 800 mg\/kg\/day), or SIH + Gal-3 inhibitor. IH exposure lasted 8 h\/day for 10 days. Outcomes included circulating SP-D, Surfactant Protein B (SP-B), inflammatory markers, physiological parameters, and histopathological lung injury scores assessed via American Thoracic Society guidelines. Results: SP-D levels showed numerical reductions with increasing IH severity (Control: 1969.07 pg\/mL [IQR: 262.15]; SIH: 1404.30 pg\/mL [IQR: 351.88]), representing a 28.6% decrease. However, between-group variability resulted in non-significant omnibus testing (Kruskal\u2013Wallis p = 0.187). Gal-3 inhibition elevated SP-D levels, particularly in severe IH (2133.95 pg\/mL [IQR: 1240.70]), though high inter-individual variability was observed (CV = 58.1%). SP-B showed significant suppression under moderate IH (p = 0.019) with restoration by treatment. Exploratory correlation analysis revealed moderate positive associations between SP-D and heart rate (r = 0.587) and respiratory rate (r = 0.419) in severe IH, though these did not reach statistical significance (p = 0.126 and p = 0.301, respectively). Histologically, severe IH induced diffuse alveolar damage (total lung score: 19.67 \u00b1 0.82). Gal-3 inhibition produced context-dependent effects: protective in severe IH but paradoxically exacerbating inflammation under moderate IH (29.20 \u00b1 4.64 vs. 20.00 \u00b1 4.34; p &lt; 0.05). Gal-3 inhibition significantly attenuated cardiac injury (injury score: 0.00 \u00b1 0.00 vs. 7.17 \u00b1 0.75 in severe IH; p &lt; 0.001, \u03b72 = 0.859). Conclusions: SP-D demonstrates severity-associated alterations consistent with alveolar epithelial stress during IH, though high variability limits definitive biomarker validation in this sample. Gal-3 inhibition modulates surfactant homeostasis and attenuates cardiopulmonary injury in a context-dependent manner. These findings support further investigation into SP-D as a component of multimodal severity stratification in OSA and highlight Gal-3 inhibition as a context-dependent anti-inflammatory strategy, pending validation in larger cohorts with tissue-level confirmation.<\/jats:p>","DOI":"10.3390\/arm94030027","type":"journal-article","created":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T14:28:23Z","timestamp":1777040903000},"page":"27","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Exploratory Changes in Surfactant Protein D During Intermittent Hypoxia and Modulation by Galectin-3 Inhibition"],"prefix":"10.3390","volume":"94","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0644-4035","authenticated-orcid":false,"given":"Saad","family":"Al-Anazi","sequence":"first","affiliation":[{"name":"Department of Physiology, College of Medicine, King Saud University, Riyadh 11461, Saudi Arabia"},{"name":"Azeer Medical Company, Jeddah 21382, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasser A.","family":"Alshawakir","sequence":"additional","affiliation":[{"name":"Experimental Surgery and Animal Laboratory, Prince Naif for Health Research Center (PNHRC), College of Medicine, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5944-8406","authenticated-orcid":false,"given":"Syed Shahid","family":"Habib","sequence":"additional","affiliation":[{"name":"Department of Physiology, College of Medicine, King Saud University, Riyadh 11461, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hayam","family":"Gad","sequence":"additional","affiliation":[{"name":"Department of Physiology, College of Medicine, King Saud University, Riyadh 11461, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asma F.","family":"Alotaibi","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alanoud T.","family":"Aljasham","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Saud University, Riyadh 12372, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wajd Ahmed","family":"Althakfi","sequence":"additional","affiliation":[{"name":"Histopathology Unit, Department of Pathology, College of Medicine, King Saud University Medical City, Riyadh 11472, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed A.","family":"Mekhtiche","sequence":"additional","affiliation":[{"name":"Department of Computer Engineering, College of Computer and Information Sciences, King Saud University, Riyadh 11543, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abeer Abdulmoati","family":"Al-Masri","sequence":"additional","affiliation":[{"name":"Department of Physiology, College of Medicine, King Saud University, Riyadh 11461, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1016\/j.jsmc.2023.05.004","article-title":"Creating an Optimal Approach for Diagnosing Sleep Apnea","volume":"18","author":"Tamisier","year":"2023","journal-title":"Sleep Med. 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