Huiwen Yang, Linlin Yang, Yingxin Liu, Linlin Wang
{"title":"Adebrelimab in Small Cell Lung Cancer: From Current Advances to Emerging Combination Strategy and Challenge.","authors":"Huiwen Yang, Linlin Yang, Yingxin Liu, Linlin Wang","doi":"10.2147/BTT.S500470","DOIUrl":"10.2147/BTT.S500470","url":null,"abstract":"<p><p>Adebrelimab is a fully humanized monoclonal antibody against programmed cell death-ligand 1 (PD-L1) that has been approved in combination with chemotherapy as the first-line treatment for extensive-stage small cell lung cancer (ES-SCLC). This approval was driven by the landmark CAPSTONE-1 trial, where adebrelimab demonstrated superior survival outcomes: median overall survival (mOS) improved from 12.8 to 15.3 months (HR=0.72, p=0.0017) and 3-year survival rates doubled (21.1% vs 10.5%) compared to chemotherapy alone. Based on this systemic treatment, addition of sequential thoracic radiotherapy achieved unprecedented mOS of 22.9 months in a Phase II trial. In limited-stage small cell lung cancer (LS-SCLC), the initial results of adebrelimab combined with concurrent chemoradiotherapy are promising. Whether in first-line or later-line treatment, there are numerous ongoing clinical trials to explore the potential of the novel adebrelimab-based regimen, and the results are highly anticipated. Despite ongoing efforts to identify biomarkers that may guide treatment decisions, no validated prognostic or predictive biomarkers are currently available for SCLC. This review summarizes the present role of adebrelimab in SCLC and outlines novel strategies aimed to further improve survival outcome.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":"19 ","pages":"365-377"},"PeriodicalIF":5.3,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12138384/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144233104","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ferdinando D'Amico, Sarah Bencardino, Fernando Magro, Axel Dignass, Ana Gutiérrez Casbas, Bram Verstockt, Ailsa Hart, Alessandro Armuzzi, Laurent Peyrin-Biroulet, Silvio Danese
{"title":"Positioning Guselkumab in The Treatment Algorithm of Patients with Crohn's Disease.","authors":"Ferdinando D'Amico, Sarah Bencardino, Fernando Magro, Axel Dignass, Ana Gutiérrez Casbas, Bram Verstockt, Ailsa Hart, Alessandro Armuzzi, Laurent Peyrin-Biroulet, Silvio Danese","doi":"10.2147/BTT.S530354","DOIUrl":"10.2147/BTT.S530354","url":null,"abstract":"<p><p>Guselkumab, a selective interleukin-23 (IL-23) inhibitor, has emerged as a promising biologic therapy for the management of patients with moderate-to-severe Crohn's disease (CD) and has been recently approved for its treatment. Unlike conventional therapies, guselkumab offers a different mechanism of action by selectively inhibiting IL-23, a key cytokine implicated in the pathogenesis of CD. IL-23 drives intestinal inflammation through activation of the Th17 cell pathway and other immune processes, positioning IL-23 inhibition as a critical therapeutic approach. In randomized Phase III clinical trials, guselkumab proved to be effective in inducing clinical and endoscopic remission both in patients naive to biologics and in patients already exposed to advanced therapies. Furthermore, no safety issues were found, supporting the well-characterized safety in other indications and its use in clinical practice also in IBD. Moreover, guselkumab has been approved for other immunomediated inflammatory disease moderate to severe plaque psoriasis, psoriatic arthritis and ulcerative colitis. This review summarizes the available evidence on efficacy and safety of guselkumab in patients with moderate to severe CD, focusing on its positioning in the treatment algorithm.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":"19 ","pages":"351-363"},"PeriodicalIF":5.3,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12136076/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144224201","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Targeting CREBRF in Cancer: Mechanistic Insights and Future Directions.","authors":"Baixue Lv, Dongdong Zhang","doi":"10.2147/BTT.S522325","DOIUrl":"10.2147/BTT.S522325","url":null,"abstract":"<p><p>Luman/CREB3 recruitment factor (LRF), also known as CREBRF, was initially identified as a cellular binding protein of Luman through yeast two-hybrid screening of a human brain cDNA library. CREBRF plays a critical role in various biological processes, with its functions garnering significant attention in the field of oncology. Notably, CREBRF is involved in endoplasmic reticulum (ER) stress and regulates the unfolded protein response (UPR), leading to an accumulation of misfolded proteins. This can ultimately result in cellular dysfunction, apoptosis, and even tumorigenesis. In solid tumors, hypoxia is a common condition, and CREBRF has been implicated in hypoxia-induced autophagy, which promotes tumor cell proliferation. Depending on the tumor type and microenvironment, CREBRF exerts diverse effects by modulating distinct signaling pathways. This review summarizes CREBRF's involvement in ER stress, cell cycle regulation, autophagy, and the mechanisms through which it influences tumor initiation and progression across various cancer types. Furthermore, the potential of CREBRF as a therapeutic target in cancer treatment is discussed, providing insights into future research and clinical applications.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":"19 ","pages":"341-350"},"PeriodicalIF":5.3,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12132502/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144214835","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Naim Ata, Hasan Satış, Orhan Küçükşahin, Erdem Karabulut, Gizem Ayan, Abdulsamet Erden, Emre Bilgin, Berkan Armağan, Duygu Tecer, Hakan Babaoğlu, Alper Sarı, Levent Kılıç, Mustafa Mahir Ülgü, Mustafa Okan Ayvalı, Şuayip Birinci, Umut Kalyoncu
{"title":"From Conventional to Advanced Therapies: A National Health Registry Report (2016-2022) on DMARDs in Rheumatoid Arthritis Treatment in Turkey.","authors":"Naim Ata, Hasan Satış, Orhan Küçükşahin, Erdem Karabulut, Gizem Ayan, Abdulsamet Erden, Emre Bilgin, Berkan Armağan, Duygu Tecer, Hakan Babaoğlu, Alper Sarı, Levent Kılıç, Mustafa Mahir Ülgü, Mustafa Okan Ayvalı, Şuayip Birinci, Umut Kalyoncu","doi":"10.2147/BTT.S507132","DOIUrl":"10.2147/BTT.S507132","url":null,"abstract":"<p><strong>Objective: </strong>There are national and international guidelines on the optimal use of disease-modifying anti-rheumatic drugs. In this study, we aimed to provide critical insights into the real-world efficacy and adherence of these DMARDs, providing a data-driven basis for optimizing treatment paradigms for RA within the national healthcare framework.</p><p><strong>Methods: </strong>This nationwide cohort study utilized data from the Turkish Ministry of Health National Electronic Database, known as E-Pulse between January 2016 and December 2022. In this analysis, cases of RA were identified using ICD-10 codes two times at least 30 days apart Treatment prescriptions were recorded based on their prescription at baseline and follow-up.</p><p><strong>Results: </strong>There were a total of 347,902 RA (79.5% female) patients in the E-Pulse system. The mean (SD) age of RA patients was 59.1 (14.8) years Methotrexate and sulfasalazine (35.1% vs 30.5%, OR 95% CI 0.81 usage was more common in men and hydroxychloroquine was more common in women 46.764 (13.4%) patients were prescribed bDMARD and/or tsDMARD 494.499 times. AntiTNF drugs are the most commonly prescribed drugs. This is followed by B-cell blockers, JAK inhibitors, anti-IL6 and T-cell blockers.</p><p><strong>Conclusion: </strong>Turkish national health database highlights the widespread use of synthetic DMARDs in treating rheumatoid arthritis (RA). While traditional DMARDs like methotrexate and hydroxychloroquine are favored the cautious use of advanced therapies, particularly anti-TNFs, suggests a potential for optimizing treatment protocols.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":"19 ","pages":"331-339"},"PeriodicalIF":5.3,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12124983/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144198250","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Guoyao Peng, Yun Zhang, Shuang Zhang, You Li, Liping Luo, Jiaxin Luo, Xinyi Nie, Hongwei Zhang, Chengcheng Liao
{"title":"Generalized Pustular Psoriasis with Cushing's Syndrome: A Case of Effective Spesolimab Treatment.","authors":"Guoyao Peng, Yun Zhang, Shuang Zhang, You Li, Liping Luo, Jiaxin Luo, Xinyi Nie, Hongwei Zhang, Chengcheng Liao","doi":"10.2147/BTT.S521363","DOIUrl":"https://doi.org/10.2147/BTT.S521363","url":null,"abstract":"<p><p>Generalized pustular psoriasis (GPP) is a rare neutrophilic skin disease characterized by persistent symptoms and sudden onset of painful, sterile pustules. These pustules may be accompanied by systemic inflammation and can be life-threatening in severe cases. Presently, there is an absence of standardized guidelines for treatment, and the majority of conventional treatments employed by clinicians are predicated on the utilization of glucocorticosteroids, immunosuppressants, and retinoids to attain anti-inflammatory and immune-suppressing effects. However, the therapeutic effect is often unsatisfactory and patients are prone to side effects. The IL-36 receptor monoclonal antibody, Spesolimab, signifies a novel therapeutic modality that has received approval from both the National Drug Administration (NMPA) of China and the US Food and Drug Administration (FDA) for the management of acute exacerbations of GPP. We report a case of a 40-year-old male patient diagnosed with GPP who had no significant improvement in symptoms and development of Cushing's syndrome after up to six months of treatment with glucocorticoids, immunosuppressants, and retinoids. The patient was treated with Spesolimab, a monoclonal antibody, resulting in a substantial improvement in symptoms. This development offers novel treatment options and provides a reference for clinical medication for patients with this particular type of GPP.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":"19 ","pages":"321-329"},"PeriodicalIF":5.3,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12077406/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144075954","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sahar S Alghamdi, Hussah N Albahlal, Raghad Saleh Alajmi, Amani Alsharidah, Aljawharah Almogren, Rasha Suliman, Zeyad I Alehaideb
{"title":"<i>Boswellia carteri</i> Birdw. Resin Extract Induces Phase-I Cytochrome P-450 Enzyme Gene Expressions in Human Hepatocarcinoma (Hep G2) Cells: In vitro and in silico Studies.","authors":"Sahar S Alghamdi, Hussah N Albahlal, Raghad Saleh Alajmi, Amani Alsharidah, Aljawharah Almogren, Rasha Suliman, Zeyad I Alehaideb","doi":"10.2147/BTT.S491278","DOIUrl":"https://doi.org/10.2147/BTT.S491278","url":null,"abstract":"<p><strong>Introduction: </strong><i>Boswellia carteri</i> (<i>B. carteri</i>) resin is widely recognized for its anti-inflammatory, wound-healing, and immunomodulatory properties. This study examines the ability of its aqueous extracts to modulate the expression of key cytochrome P450 (CYP) enzymes-CYP1A2, CYP2B6, and CYP3A4-in Hep G2 cells, emphasizing pharmacokinetic and toxicological implications.</p><p><strong>Methods: </strong>Aqueous extracts were evaluated for endotoxin contamination and cytotoxicity to ensure suitability for in vitro experimentation. PCR analysis was employed to quantify CYP enzyme gene expression. Computational tools, including Protox-II, Swiss ADME, and molecular docking, were used to assess pharmacokinetics, CYP interactions, and biological targets. Competitive binding assays were performed to investigate the involvement of the constitutive androstane receptor (CAR) in CYP induction.</p><p><strong>Results: </strong>The results suggest that several metabolites, particularly ursodeoxycholic acid and beta-sitosterol, show potential interactions with CYP enzymes, with ursodeoxycholic acid demonstrating the highest probability of biological effects on CYP and a strong binding affinity to the Constitutive Androstane Receptor (CAR). Moreover, a receptor competitive binding assay suggested that the primary mechanism of CYP 2B6 and 3A4 induction is through activation of the CAR receptor although additional confirmatory studies are necessary.</p><p><strong>Discussion: </strong>The observed CYP enzyme induction through CAR receptor activation aligns with USFDA guidelines for CYP studies. However, the hepatotoxic potential of ursodeoxycholic acid and the associated toxicity risks of other metabolites underscore the need for caution. The findings highlight the potential for herb-drug interactions, particularly with pharmaceuticals metabolized by CYP enzymes.</p><p><strong>Conclusion: </strong>In conclusion, there is a potential for interactions between <i>B. carteri</i> resins and pharmaceuticals metabolized by CYP enzymes; thus, we advise caution to consumers, patients, and healthcare providers regarding their concomitant use. Although our findings provide valuable insights, further in vivo studies are essential to validate the modulatory effects of <i>B. carteri</i> on CYP gene expression.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":"19 ","pages":"289-320"},"PeriodicalIF":5.3,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12063698/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143959575","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"OX40/OX40L as a Therapeutic Target in Atopic Dermatitis: A Scoping Review.","authors":"Fernando Valenzuela, Victor Meza","doi":"10.2147/BTT.S511125","DOIUrl":"https://doi.org/10.2147/BTT.S511125","url":null,"abstract":"<p><p>Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin disease, whose pathophysiology involves a complex interplay of genetic and environmental factors that lead to dysregulated T-cell-mediated inflammatory pathways and a compromised skin barrier. Despite the recent introduction of novel targeted therapies for moderate-to-severe AD, many patients still fail to achieve or maintain treatment goals, or experience treatment-emergent adverse events, which continue to burden their disease management. Recently, the role of T cell co-stimulatory molecule OX40 and its ligand OX40L, which is mainly expressed on professional antigen-presenting cells such as dendritic cells, has attracted widespread research attention as a potential therapeutic target in T cell-mediated skin diseases. Moreover, early basic and clinical research has shown encouraging results regarding the efficacy and safety of therapies targeting the OX40-OX40L axis in moderate-to-severe AD. Therefore, herein we aim to summarize the current evidence regarding the efficacy and safety of inhibiting the OX40/OX40L signaling axis in patients with moderate-to-severe AD.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":"19 ","pages":"281-288"},"PeriodicalIF":5.3,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12054532/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143959579","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Silvana Ancona, Katherine Armstrong, Chiara Longo, Rosalind Rabone, Victoria Merrick, Paul Henderson, Paolo Gandullia, David C Wilson, Serena Arrigo, Richard K Russell
{"title":"Adalimumab Biosimilars Demonstrate Long-Term Durability and Cost-Effectiveness in Paediatric Inflammatory Bowel Disease: A Real-World Two-Centre European Cohort Study.","authors":"Silvana Ancona, Katherine Armstrong, Chiara Longo, Rosalind Rabone, Victoria Merrick, Paul Henderson, Paolo Gandullia, David C Wilson, Serena Arrigo, Richard K Russell","doi":"10.2147/BTT.S511248","DOIUrl":"https://doi.org/10.2147/BTT.S511248","url":null,"abstract":"<p><strong>Purpose: </strong>Adalimumab biosimilars are increasingly used in paediatric Inflammatory Bowel Disease (PIBD), but data remain limited. This study assessed their durability, efficacy, safety and cost implications in PIBD.</p><p><strong>Patients and methods: </strong>Consecutive PIBD patients who started adalimumab biosimilars between October 2018 and December 2023 at two centres in Scotland and Italy, with at least 6 months follow-up, were included. Demographic, disease, treatment, and adverse event data were collected. Disease activity was assessed at baseline, 6, 12, 24, 36 months, and at last follow-up. Durability was evaluated using Kaplan-Meier analysis.</p><p><strong>Results: </strong>In total 130 patients (81 males; median age 12.3 years) were included (115 Crohn's Disease, 7 Ulcerative Colitis, 8 IBD unclassified). The biosimilars were ABP 501 (85%), GP2017 (14%), SB5 (1%); 41 (32%) patients switched from originator. After a median follow-up of 26 months, 87/130 (67%) patients remained on biosimilars, while 43 discontinued at a median of 14 months. Durability probabilities were 93%, 86%, 75%, 62%, and 57% at 6, 12, 24, 36, and 54 months, respectively. Patients previously exposed to ADA originator had a lower risk of biosimilar failure (hazard ratio, adjusted for age at diagnosis: 0.51 [95% confidence interval: 0.26-0.99], p=0.047). Trough levels ≥11.6 μg/mL at 6 months were associated with greater durability (<i>AUC=0.68, p=0.007)</i>. Adverse events occurred in 46/130 patients, mainly psoriasis and injection site reactions (13% each), with one lymphoma. Estimated cost savings were 5,030€ per patient/year.</p><p><strong>Conclusion: </strong>This real-life study demonstrated high durability and remission rates for adalimumab biosimilars in PIBD, confirming their clinical, cost-effectiveness and safety profile in children.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":"19 ","pages":"265-279"},"PeriodicalIF":5.3,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12049108/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143963132","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Epigenetic Regulation of Sorbitol Dehydrogenase in Diabetic Retinopathy Patients: DNA Methylation, Histone Acetylation and microRNA-320.","authors":"Ramzi Amin, Hikmat Permana, Arief Sjamsulaksan Kartasasmita, Dany Hilmanto, Rachmat Hidayat","doi":"10.2147/BTT.S521519","DOIUrl":"https://doi.org/10.2147/BTT.S521519","url":null,"abstract":"<p><strong>Purpose: </strong>This study aimed to investigate the correlation between epigenetic markers and sorbitol dehydrogenase (SDH) levels in patients with type 2 diabetes and diabetic retinopathy (DR).</p><p><strong>Patients and methods: </strong>We conducted a case control study on 40 patients with type 2 diabetes and DR and 40 patients with type 2 diabetes without DR. Clinical data and ophthalmological examinations were performed to confirm the presence or absence of DR. Blood samples were collected for the analysis of DNA methylation, histone acetylation, microRNA-320 levels, and SDH enzyme activity. The epigenetic markers were evaluated using enzyme linked immunosorbent modified assay. The data were analyzed using statistical tests, including Spearman correlation and multiple linear regression.</p><p><strong>Results: </strong>In patients with DR, there was a significant negative correlation between microRNA-320 levels and SDH enzyme activity (r=-0.968, p=0.000). No significant correlations were found between DNA methylation or histone acetylation and SDH activity. Multivariate analysis confirmed the strong negative correlation between microRNA-320 and SDH (r = -0.727, p=0.000), with microRNA-320 explaining 58.1% of the variance in SDH levels.</p><p><strong>Conclusion: </strong>The findings suggest that microRNA-320 plays a crucial role in regulating SDH enzyme activity in patients with type 2 diabetes and DR. The development of microRNA-320-based therapies, such as miRNA mimics or antagomirs, may offer a novel approach to modulating SDH activity and mitigating the detrimental effects of the polyol pathway in DR. Further researches are needed to validate the results and mechanism underlying the correlation between epigenetic regulation SDH in DR.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":"19 ","pages":"251-264"},"PeriodicalIF":5.3,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12048750/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143967855","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Whole Transcriptome-Based ceRNA Regulatory Network Analysis of Radiation-Induced Esophageal Epithelial Cell Injury.","authors":"Hongyu Lin, Yahui Feng, Hangfeng Liu, Jinkang Zhang, Xiaolin Zhang, Xue Ying, Yuhong Shi, Hao Tan, Wenling Tu","doi":"10.2147/BTT.S496064","DOIUrl":"https://doi.org/10.2147/BTT.S496064","url":null,"abstract":"<p><strong>Introduction: </strong>Esophageal epithelial cells are essential for esophageal homeostasis and defense against harmful stimuli, but the mechanisms of radiation-induced injury in these cells are poorly understood. The competitive endogenous RNA (ceRNA) network, involved in various physiological processes and diseases, may also play a role in radiation-induced injury, although its mechanism remains unclear. This study aimed to investigate the effects of ionizing radiation on human esophageal epithelial cells and explore the role of the ceRNA network in this injury.</p><p><strong>Methods: </strong>Cellular phenotype experiments assessed the effects of ionizing radiation on human esophageal epithelial cells. Whole transcriptome sequencing (lncRNA, circRNA, miRNA, and mRNA) was performed on cells exposed to 0, 2, and 4 Gy radiation. Differentially expressed RNAs (dd-DERs) were identified through differential expression analysis and dose-dependent screening. A ceRNA network was constructed using co-expression analysis and binding site prediction. Real-time quantitative PCR validated the expression levels of selected dd-DERs, and gene set enrichment analysis explored affected pathways.</p><p><strong>Results: </strong>We identified 41 lncRNAs, 18 miRNAs, and 192 mRNAs as dose-dependent differentially expressed RNAs. A ceRNA network comprising 10 lncRNAs, 5 miRNAs, and 55 mRNAs was established. Real-time PCR confirmed the expression levels of 8 dd-DERs within the network. Gene set enrichment analysis showed that radiation disrupted channel activity, cell replication, repair, and immune response. Functional enrichment analysis revealed modulation of metabolic pathways, particularly involving UGT1A family members.</p><p><strong>Discussion: </strong>This study established a ceRNA network related to radiation-induced esophageal epithelial cell injury, advancing our understanding of its pathophysiology. The ceRNA network may mediate injury through metabolic pathway modulation. Future work should focus on elucidating specific ceRNA interactions and exploring therapeutic potential for mitigating radiation-induced esophageal injury.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":"19 ","pages":"231-249"},"PeriodicalIF":5.3,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12034488/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143964249","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}