International Journal of Molecular Sciences最新文献

{"title":"Organ-Specific Phenolic Specialization and Antioxidant Responses in <i>Crocus cancellatus</i>: LC-MS/MS and Multivariate Analysis.","authors":"Bedrettin Selvi","doi":"10.3390/ijms27198904","DOIUrl":"10.3390/ijms27198904","url":null,"abstract":"<p><p>Organ-specific allocation of phenolic metabolites may shape antioxidant responses in <i>Crocus</i> species. This study characterized stamen, pistil, tepal, perigon tube, and corm of <i>Crocus cancellatus</i> Herb. using ultrasound-assisted methanolic extraction, liquid chromatography-tandem mass spectrometry with 30 authentic standards, six antioxidant assays, a relative antioxidant capacity index, Pearson correlation analysis, and principal component analysis. Twenty phenolic compounds were quantified. Hesperidin predominated in all organs and was highest in the tepal (17,660 ± 60 μg/g extract), approximately 43-fold above the corm. The pistil contained the highest 3-hydroxybenzoic acid (331 ± 1 μg/g extract) and 4-hydroxybenzoic acid (341 ± 2 μg/g extract), whereas the corm was enriched in pinoresinol (60.1 ± 0.8 μg/g extract) and uniquely contained vanillin (16.0 ± 0.6 μg/g extract). The tepal showed the highest total flavonoid content (81.50 ± 0.40 mg RE/g extract), while the stamen had the highest total phenolic content (12.63 ± 0.05 mg GAE/g extract). The corm showed the strongest DPPH radical scavenging (IC₅₀ = 3.96 mg/mL), whereas the pistil led in ABTS and FRAP responses. Principal component analysis explained 64.16% of total variance and separated the five organ profiles. These findings demonstrate organ-specific phenolic specialization and support targeted bioactivity studies.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"27 19","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13664975/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149193512","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Progesterone Modulates Protein Synthesis in Osteoarthritic Fibroblast-like Synoviocytes.","authors":"Fadi Askar, Georgios Chatziagorou, Sofia Wüstenhagen, Alessia Capraro, Björn Andersson, Evelin Berger, Daniela Esposito, Luminita Labusca, Carmen Corciulo","doi":"10.3390/ijms27198899","DOIUrl":"10.3390/ijms27198899","url":null,"abstract":"<p><p>Knee osteoarthritis (OA) is highly prevalent in women and is characterized by structural joint alterations and synovial inflammatory processes that contribute to pain and impaired mobility. In a previous study, we identified a positive correlation between progesterone levels and pain intensity in postmenopausal women. However, the role of progesterone in synovial inflammation remains poorly understood. Therefore, this study aimed to characterize sex-specific differences in synovial tissue between postmenopausal women and age-matched men and to investigate the association between progesterone levels and the identified molecular profile. Whole blood and synovial tissue were collected from women and men with knee OA to assess plasma progesterone concentrations and the proteomic profiles of synovial tissue and isolated primary fibroblast-like synoviocytes (FLSs). The expression and localization of progesterone receptors were evaluated using RNAscope and immunofluorescence. FLS stimulated with physiological concentrations of progesterone were used for de novo protein synthesis assays. Quantitative proteomics of synovial tissue revealed enrichment of protein synthesis-related pathways in women compared to age-matched men, and isolated FLS from women with knee OA exhibited a pro-inflammatory and pro-fibrotic proteomic profile. Stratification by plasma progesterone levels identified two distinct patient groups, where lower progesterone levels were associated with pro-inflammatory signatures. The RNAscope analysis demonstrated increased transcriptional activity in synovial tissue from women with knee OA, localized to CD90⁺ sublining FLS. However, progesterone receptor expression at both the RNA and protein levels showed no sex-specific differences. Moreover, physiological concentrations of progesterone inhibited <i>de novo</i> protein synthesis in FLS isolated from men with knee OA. These findings underscore the hormonal context-dependent modulatory effects of progesterone on synovial inflammation and fibroblast activity. The study further highlights the importance of incorporating sex-specific hormonal profiles into OA patient stratification to support more precise and targeted therapeutic strategies.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"27 19","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13664916/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149193590","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"microRNA and Regulatory Networks of Human Macrophage During <i>Leishmania major</i> In Vitro Infection.","authors":"Sara Habouria, Aymen Bali, Aurora Diotallevi, Ali Ben-Cheikh, Chiraz Atri, Mauro De Santi, Sara Maestrini, Luca Galluzzi, Dhafer Laouini, Fatma Zahra Guerfali","doi":"10.3390/ijms27198893","DOIUrl":"10.3390/ijms27198893","url":null,"abstract":"<p><p><i>Leishmania</i> (<i>L.</i>) <i>major</i> modulates host microRNA (miR) expression to promote intracellular survival, yet the roles of specific miRs during early infection of human macrophages remain poorly defined. We investigated the dynamic regulation of miR-21-5p and miR-146a-5p in THP-1-derived macrophages infected with <i>L. major</i> over an early post-infection time course (3-48 h), alongside miR-30a-3p and miR-101-3p. Both miR-21-5p and miR-146a-5p were significantly upregulated during the early stages of infection (3-24 h) before declining by 48 h. Using antisense LNA inhibitors, we achieved independent single and dual silencing of both miRs, allowing us to dissect their functional contribution to host gene expression. In silico network analysis identified 887 shared and specific target genes, including NFKB1, MYC, STAT3, HIF1A, TNF, CXCL8, IL18, and XBP1. Silencing of miR-21-5p and miR-146a-5p at early time points relieved inhibitory control over several of these targets, notably increasing NF-κB, MYC, IL18 and XBP1 expression, and reducing TNF and sXBP1, consistent with their role as negative regulators of innate immune signaling. These findings identify miR-21-5p and miR-146a-5p as early, dynamic regulators of the human macrophage transcriptional response to <i>L. major</i> infection and identify their target genes as candidate biomarkers and therapeutic targets in cutaneous leishmaniasis.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"27 19","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13666224/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149193160","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cerium Dioxide Nanoparticles Modulate Ribosomal DNA Transcriptional Activity in Cultured Human Skin Fibroblasts.","authors":"Natalia N Veiko, Elizaveta S Ershova, Madina M Sozarukova, Elena V Proskurnina, Larisa V Kameneva, Edmund V Kostyuk, Tatiana M Rozhnova, Yuriy L Orlov, Svetlana Yu Vikhrova, Alesya M Drozhdinina, Vladimir K Ivanov, Svetlana V Kostyuk","doi":"10.3390/ijms27198913","DOIUrl":"10.3390/ijms27198913","url":null,"abstract":"<p><p>The study investigates the effect of cerium dioxide (CeO₂) nanoparticles on ribosomal DNA (rDNA) transcriptional activity and the status of ribosomal genes in human skin fibroblasts. Nano-CeO₂ has attracted attention due to its antioxidant and redox properties; however, its impact on rDNA has so far remained virtually unexplored. Fibroblasts from ten adult donors were incubated with nano-CeO₂ for 3 and 24 h, and the copy number of ribosomal genes and their functional state were assessed using real-time quantitative PCR and non-radioactive quantitative hybridization; the interaction of the nanoparticles with the cells was also assessed by fluorescence microscopy. It was shown that exposure to CeO₂ nanoparticles leads to functional changes in rDNA transcription and rRNA abundance, indicating modulation of ribosomal biogenesis and consistent with a model of altered balance between transcriptionally active and inactive rDNA copies, although this study did not directly measure ribosome content or rDNA fraction distribution. The observed effects are likely mediated by the antioxidant and redox properties of the nanoparticles. Thus, nano-CeO₂ can be considered a compound capable of modulating the functional state of ribosomal genes in normal human cells.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"27 19","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13665379/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149193358","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhancing the Activity of Ribokinase from <i>Thermus</i> sp. 2.9 Through Rational Design for the Cascade Synthesis of Modified Nucleotides and Nucleosides.","authors":"Evgeniy A Zayats, Yulia A Abramchik, Maria A Kostromina, Ilya V Fateev, Andrey A Karanov, Alexandra R Sharafutdinova, Vasiliy A Ptushkin, Irina D Konstantinova, Andrey V Golovin, Roman S Esipov","doi":"10.3390/ijms27198911","DOIUrl":"10.3390/ijms27198911","url":null,"abstract":"<p><p>The pursuit of efficient approaches for the production of promising antiviral and cytostatic pharmaceuticals is a crucial direction in medical biotechnology, especially after the COVID-19 pandemic. Modified nucleosides and nucleotides represent a highly promising class of chemicals for the development of drugs against cancer and viral infections. Being an alternative to traditional chemical synthesis, cascades of nucleic exchange enzymes offer single-step synthesis of such compounds with exceptional stereo- and regioselectivity. Furthermore, employing thermostable enzymes for such cascades offers the advantages of increased substrate solubility, lower solution viscosity, prevention of contamination, and simplified biocatalyst purification via thermal denaturation. The first biocatalyst for two distinct cascade pathways of nucleotide and nucleoside synthesis is ribokinase. In this article, we report improving the activity of ribokinase from <i>Thermus</i> sp. 2.9 (<i>Tsp</i>RK) for the cascade synthesis of modified nucleosides and nucleotides. We have employed a rational design approach, including Boltz-2 modeling and sequence conservation analysis. We have engineered two mutants, T244I and N272H, achieving a 3-fold increase in ribose phosphorylation rate (<i>k_cat</i>). Improving the enzymatic activity of a thermostable ribokinase will serve as the basis for further optimization of cascade synthesis of pharmaceutical modified nucleosides and nucleotides.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"27 19","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13665051/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149193453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of Triacetin- and Tributyrin-Based Formulations on IBS Microbiome Composition and SCFA Profiles: A Preclinical Study.","authors":"Liam Jenkins Sánchez, Jonas Poppe, Aurélien Baudot, Lam Dai Vu, Will Villella, Pieter Van den Abbeele","doi":"10.3390/ijms27198910","DOIUrl":"10.3390/ijms27198910","url":null,"abstract":"<p><p>Irritable bowel syndrome (IBS) is a prevalent yet poorly understood functional gut disorder frequently associated with microbial dysbiosis, making microbiome-targeting interventions a promising management strategy. In this study, we evaluated the microbiome-modulating potential of three doses of triacetin (TA; ReBiome™; 100, 200 and 300 mg/day) and two finished formulations containing TA and/or tributyrin (TB): Active Biome™ (AB) and Bio Complete 3™ (BC3). Inulin served as a benchmark prebiotic. The validated ex vivo Systemic Intestinal Fermentation Research (SIFR^®) technology pipeline was applied using fecal microbiota from eight adults with IBS. TA dose-dependently increased short-chain fatty acid (SCFA) levels from 100 mg/day, significantly increasing acetate and butyrate while maintaining low gas formation. In addition to acetate and butyrate, AB and BC3 also promoted propionate while BC3 induced a particularly pronounced butyrate increase. Overall, both formulations induced stronger SCFA but milder gas increases than inulin. TA, AB and BC3 enriched IBS-depleted, butyrate-associated OTUs related to <i>Faecalibacterium</i> and <i>Anaerobutyricum</i> species. AB and BC3 increased microbial diversity (community modulation score (CMS)) by promoting Bifidobacteriaceae, Lachnospiraceae and Bacteroidaceae. Overall, TA and TA/TB-containing formulations promoted butyrate production, potentially helping mitigate IBS symptom severity by inducing a favorable fermentation profile with limited gas formation.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"27 19","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13665126/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149193578","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cellular and Tissue Mechanisms of Laser-Assisted Regeneration of Tympanic Membrane Perforation.","authors":"Ekaterina Valerievna Blinova, Igor Vyacheslavovich Lunyov, Andrey Igorevich Osipyants, Kirill Dmitrievich Blinov, Anna Vladimirovna Zolotova, Liudmila Mikhailovna Ignatova, Valeriy Michailovich Svistushkin, Valeria Vadimovna Gainutdinova, Mikhail Valerievich Svistushkin, Ekaterina Mikhailovna Kasianenko, Alexander Ivanovich Omelchenko, Aleksey Vasilevich Yuzhakov, Olga Igorevna Baum","doi":"10.3390/ijms27198906","DOIUrl":"10.3390/ijms27198906","url":null,"abstract":"<p><p>Chronic tympanic membrane (TM) perforations remain a significant clinical problem due to limited spontaneous healing and the drawbacks of surgical interventions. The present study aimed to evaluate the effects of low-intensity infrared laser irradiation on cellular mechanisms of regeneration and to assess its therapeutic potential in TM repair. Primary fibroblast cultures isolated from chinchilla tissue were exposed to laser radiation at wavelengths 1560 nm and 1450 nm. Cellular responses were analyzed using MTT assay, scratch test, Ki-67 immunostaining, and ELISA for collagen type II. In addition, an in vivo model of chronic TM perforation in chinchillas was used to validate the regenerative effects under physiological conditions. Laser irradiation was associated with accelerated scratch closure and increased extracellular matrix production under selected irradiation conditions, whereas metabolic and proliferative indices decreased over time, most likely reflecting culture confluence and maturation rather than cytotoxicity. In vivo, complete closure of tympanic membrane perforations was observed in all laser-treated ears in the context of collagen sponge-assisted repair, whereas scaffold-only control perforations remained unclosed. These findings support the potential of low-intensity infrared laser irradiation as a minimally invasive adjunct to scaffold-assisted tympanic membrane repair. However, the proposed involvement of endogenous progenitor cell populations should be regarded as a hypothesis requiring further histological and marker-based validation.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"27 19","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13666236/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149193340","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Conserved and Promoter-Specific <i>Cis</i>-Regulatory Features of Digestion-Associated Chitinase Genes in <i>Droseraceae</i>.","authors":"Martin Jopčík, Monika Danchenko, Ľubomír Harenčár, Jana Libantová","doi":"10.3390/ijms27198907","DOIUrl":"10.3390/ijms27198907","url":null,"abstract":"<p><p>Carnivorous plants recruit defense-related pathways for prey digestion, yet the <i>cis</i>-regulatory architecture underlying their expression remains poorly characterized. In addition to herbivore and fungal pathogen responses, chitinases play an important role in plant carnivory. We analyzed promoters of glycoside hydrolase family 19 (GH19) class I chitinase genes in the Droseraceae family, which are the most abundant chitinases associated with prey digestion. Promoters of newly identified putative class I chitinases found in <i>Drosera spatulata</i>, <i>Drosera tokaiensis</i>, and <i>Aldrovanda vesiculosa</i> were also examined. Core promoter features, <i>cis</i>-regulatory elements, transcription factor binding site (TFBS) profiles, <i>de novo</i> motifs, and promoter sequence divergence were assessed. Within the sampled promoter set, no single <i>cis</i>-element or transcription factor family-compatible pattern was shared by all carnivorous promoters while being absent from <i>Arabidopsis</i> reference promoter. Instead, Droseraceae promoters showed candidate ATG-relative positional configurations of shared stress-, defense-, and hormone-responsive elements, including a distal MYC/E-box-compatible-proximal W-box pattern, while an ordered DRE-W-box-ERE configuration occurred in six sundew promoters. The TFBS profiling revealed promoter-specific differences in the representation of loci compatible with bHLH-family models, WRKY, MYB, MYB-related, NAC, and HSF models. Together, these analyses identify candidate promoter-specific patterns and provide a foundation for further broader comparative and functional validation.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"27 19","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13665433/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149193389","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of Genes Accurately Predicting Fiber Length for AI-Powered Gene-Based Breeding Across Populations and Environments in Cotton.","authors":"Yuan Ye, Yun-Hua Liu, C Wayne Smith, Sing-Hoi Sze, Hong-Bin Zhang","doi":"10.3390/ijms27198908","DOIUrl":"10.3390/ijms27198908","url":null,"abstract":"<p><p>AI-powered gene-based breeding (AI-GBB) has the potential to be a next-generation breeding technology. However, it is unclear whether agronomic genes identified with one population can be reliably used for AI-GBB across diverse populations, environments, and eco-agriculture systems. We evaluated 474 cotton fiber length (<i>GFL</i>) genes using two diverse populations grown across 11 environments in China and the United States. Four hundred and seventy-five functional SNPs significantly impacting fiber length were identified from 143 of the genes and tested for AI-GBB. Either the 475 functional SNPs or their 143 SNPs with one SNP per gene predicted fiber lengths across environments using either the total number of their favorable alleles or themselves as DNA markers at accuracies of 0.75-0.89, outperforming genomic selection by several times. The prediction model trained in one environment accurately and consistently predicted fiber length in all other environments. We found that the <i>GFL</i> genes enriched in proteolysis, protein binding, and UDP-sugar pyro-phosphorylases play important roles in their predictability. Our results demonstrate that agronomic genes identified from one population can be robust predictors of quantitative traits across diverse populations and environments for AI-GBB. The functional SNPs provide the most desirable tools for enhanced cotton breeding with all molecular breeding methods developed to date, and the utility knowledge of the genes is necessary for the development and deployment of AI-GBB in all crops.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"27 19","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13665504/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149193572","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CFTR Functional Rescue and Heterogeneous Clinical Outcomes Following Elexacaftor/Tezacaftor/Ivacaftor Therapy in People with Cystic Fibrosis Carrying the W1282R Variant.","authors":"Elena Kondratyeva, Anna Efremova, Yuliya Melyanovskaya, Elena Zhekaite, Maria Sapelnikova, Michael Milovanov, Olga Shchagina, Anna Voronkova, Victoria Sherman, Stanislav Krasovsky, Sergey Kutsev, Dmitry Goldshtein","doi":"10.3390/ijms27198896","DOIUrl":"10.3390/ijms27198896","url":null,"abstract":"<p><p>The clinical response to elexacaftor/tezacaftor/ivacaftor (ETI) in people with cystic fibrosis carrying the rare cystic fibrosis transmembrane conductance regulator (CFTR) variant W1282R has not been well characterized. We retrospectively analyzed 12 people with cystic fibrosis treated with ETI for 3-36 months in addition to ongoing standard CF therapy. Baseline lung function was generally preserved in patients with available spirometry (median percent predicted forced expiratory volume in 1 s (ppFEV₁), 110%; interquartile range (IQR), 93-123), limiting the potential for further improvement in ppFEV₁; no statistically significant change in ppFEV₁ was detected during ETI therapy (<i>p</i> = 0.328). Paired data for ppFEV₁, body mass index (BMI), and sweat conductivity were available for 8, 12, and 9 patients, respectively. CFTR function was assessed by intestinal current measurement (ICM; <i>n</i> = 4) and patient-derived intestinal organoids (<i>n</i> = 2). Functional testing demonstrated markedly reduced baseline CFTR activity. In the patient with paired ICM measurements before and during ETI therapy, restoration of CFTR-mediated chloride transport was observed, whereas ETI significantly increased forskolin-induced swelling (FIS) in both patient-derived organoid cultures (<i>p</i> < 0.001 for each culture). BMI did not change significantly during ETI therapy (<i>p</i> = 0.269). Sweat conductivity showed a statistically significant overall reduction (median change, -3 mmol/L; <i>p</i> = 0.031); however, marked reductions were observed in only two of nine patients. Interpretation is limited by the small retrospective cohort and incomplete availability of paired clinical and functional data. These findings indicate that functional responsiveness of W1282R-CFTR to ETI may not be accompanied by consistent improvement across the clinical outcomes assessed.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"27 19","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13665084/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149193454","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}