Biologics : Targets & Therapy最新文献

{"title":"Beyond Eczema Control: Long-Term Outcomes of Dupilumab Therapy in Six Patients with Netherton Syndrome.","authors":"Kamila Zawadzińska-Halat, Magdalena Stec, Katarzyna Poznańska-Kurowska, Maciej Pastuszczak","doi":"10.2147/BTT.S638248","DOIUrl":"10.2147/BTT.S638248","url":null,"abstract":"<p><p>Netherton syndrome is a rare and severe genodermatosis caused by pathogenic variants in <i>SPINK</i>5, leading to epidermal barrier dysfunction, immune dysregulation, and prominent atopic manifestations. Therapeutic options remain limited, and long-term real-world data on biologic treatment are scarce. We report a retrospective two-center real-world case series of six patients with Netherton syndrome treated with dupilumab, with emphasis on long-term outcomes, safety, and clinical effects beyond eczema control. Five patients were managed at one dermatology referral center and one patient at a second center. Clinical data were collected retrospectively from medical records, including disease severity scores, pruritus, quality of life, genetic findings, comorbidities, treatment duration, adverse events, and additional clinically relevant observations. Dupilumab was initiated because of severe, chronic, and refractory inflammatory skin disease with intense pruritus and impaired quality of life. Follow-up ranged from 13 to 34 months. All patients achieved sustained, clinically meaningful improvement in inflammatory skin lesions, pruritus, and quality of life, although complete remission was not observed. Treatment was well tolerated, including in patients with recurrent infections, immunodeficiency-like features, severe food allergy, and a history of acute lymphoblastic leukemia. Additional observations included improvement in hair abnormalities and sweating in selected patients, reduced infectious burden, improved growth parameters, and absence of further anaphylactic episodes in one patient. These findings suggest that dupilumab may represent a valuable long-term therapeutic option for Netherton syndrome with prominent type 2 inflammatory features. Potential benefits beyond eczema control should be regarded as hypothesis-generating and require confirmation in larger multicenter studies.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":"20 ","pages":"638248"},"PeriodicalIF":4.5,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13674243/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149215047","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":"Real-World Outcomes of a Non-Medical Switch to Adalimumab-Atto Biosimilar: Safety, Effectiveness, and Treatment Persistence in an Adult Saudi Tertiary Care Population.","authors":"Alhanouf Almousa, Mohamed Ahmed, Rayd Abdulaziz Almehizia, Meshal Aldurayhim, Gamal Mohamed, Almutairdi Abdulelah, Yousef Binamer, Ahmed Alshaikh","doi":"10.2147/BTT.S612345","DOIUrl":"10.2147/BTT.S612345","url":null,"abstract":"<p><strong>Background: </strong>Adalimumab-atto, a biosimilar to adalimumab, has been widely adopted for managing autoimmune conditions due to its demonstrated safety, efficacy, and cost-effectiveness in clinical trials. However, real-world data from Saudi Arabian population remains limited.</p><p><strong>Objective: </strong>This study aimed to evaluate the persistence, safety, and clinical outcomes of patients transitioned from originator adalimumab (Humira^®) to adalimumab-atto biosimilar (Amgevita^®) at a tertiary care center.</p><p><strong>Methods: </strong>A retrospective self-controlled cohort study was conducted, including all patients transitioned to adalimumab-atto between January 1 and December 31, 2022, for non-medical reasons. The primary endpoint was treatment persistence at 12 months. Secondary endpoints included disease stability, adverse events, and reasons for discontinuation.</p><p><strong>Results: </strong>The study included 265 adult patients previously treated with originator adalimumab. The mean age of the cohort was 41 ± 13 years, with 46.8% being female. The most common indications were Crohn's disease (40.4%), rheumatoid arthritis (16.6%), and plaque psoriasis (12.1%), with a mean disease duration of 11.7 ± 6.7 years. At 12 months, 90.2% of patients persisted with adalimumab-atto, of whom 79.5% remained stable, while 20.5% were classified as unstable Twenty-six patients (9.8%) discontinued therapy, primarily due to insufficient efficacy (13 patients), with one discontinuation attributed to adverse events.</p><p><strong>Conclusion: </strong>Adalimumab-atto demonstrated high treatment persistence and favorable safety outcomes in a diverse population of patients with autoimmune diseases. These findings support the feasibility of continued use of the biosimilar in patients with immune-mediated diseases.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":"20 ","pages":"612345"},"PeriodicalIF":4.5,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13674635/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149214997","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":"Apatinib Plus PD-1 Blockade versus Chemotherapy After Prior Immunotherapy in Advanced Gastric or Gastroesophageal Junction Adenocarcinoma: A Retrospective Cohort Study.","authors":"Rui-Xin Li, Hong-Wei Yang, Yun-Fei Zhang, Xin-Yu Liu","doi":"10.2147/BTT.S639872","DOIUrl":"10.2147/BTT.S639872","url":null,"abstract":"<p><strong>Objective: </strong>To compare clinical outcomes and safety of apatinib plus programmed death-1 (PD-1) blockade versus single-agent chemotherapy in patients with advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma previously exposed to immune checkpoint inhibitors (ICIs).</p><p><strong>Methods: </strong>This single-center retrospective cohort included 117 adults with HER2-negative advanced G/GEJ adenocarcinoma treated after discontinuation of an ICI-containing regimen. 59 patients received apatinib plus PD-1 blockade (AP group) and 58 received single-agent chemotherapy (CT group). The primary endpoint was overall survival (OS), secondary endpoints included progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), duration of response (DoR), and treatment-related adverse events (TRAEs). Survival was analyzed using Kaplan-Meier methods and Cox regression, stabilized inverse probability of treatment weighting (IPTW) and prespecified sensitivity analyses were used to assess robustness to measured confounding.</p><p><strong>Results: </strong>ORR was numerically higher in the AP group than in the CT group (20.3% vs 8.6%, <i>P</i>=0.072). The DCR was significantly higher in AP group (71.2% vs 36.2%, <i>P</i><0.001). Among the responders, median DoR was 5.2 months in the AP group and 2.6 months in the CT group (<i>P</i><0.001). Median PFS was 4.5 months in AP group and 2.8 months in CT group (HR=0.58, 95% CI: 0.39-0.88, <i>P</i>=0.008). Median OS was 11.3 and 6.4 months, respectively (HR=0.55, 95% CI: 0.36-0.83, <i>P</i>=0.004). Multivariable Cox and stabilized IPTW analyses yielded directionally consistent survival associations (IPTW: OS HR=0.53, 95% CI: 0.36-0.79; PFS HR=0.57, 95% CI: 0.39-0.85). Any-grade TRAEs occurred in 86.4% and 91.4% of patients in AP and CT group, respectively. Grade ≥3 TRAEs occurred in 39.0% and 55.2%, respectively.</p><p><strong>Conclusion: </strong>Apatinib plus PD-1 blockade was associated with longer survival and greater disease control than single-agent chemotherapy. Given the single-center retrospective design, limited sample size, treatment heterogeneity, incomplete biomarker characterization, and potential residual confounding, these findings are hypothesis-generating, do not establish causality, and require prospective validation.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":"20 ","pages":"639872"},"PeriodicalIF":4.5,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13621946/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149079609","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":"Oral Acitretin Combined with Topical 0.1% Tretinoin Cream for Facial Basal Cell Carcinoma in an Elderly Patient: A Case Report.","authors":"Zhirong Shu, Yu Jiang, Shilin Deng, Tingnan Chen, Jingyao Liang, Xibao Zhang","doi":"10.2147/BTT.S617054","DOIUrl":"https://doi.org/10.2147/BTT.S617054","url":null,"abstract":"<p><p>Basal cell carcinoma (BCC) is the most common skin malignancy, and surgical excision remains the first-line treatment for most lesions. However, therapeutic options for elderly patients who are unsuitable for or decline surgery are limited. Acitretin, a systemic retinoid, has shown potential antitumor effects, while topical tretinoin may enhance local therapeutic efficacy. We herein report an elderly patient with facial BCC presenting as an ulcerative lesion on the right forehead. Reflectance confocal microscopy revealed basaloid cells arranged in cord-like structures, and histopathological examination demonstrated nests of basaloid tumor cells with peripheral palisading and retraction clefts, confirming the diagnosis of nodular BCC. The patient was treated with oral acitretin in combination with topical 0.1% tretinoin cream. After 12 weeks of treatment, the ulcerative lesion showed near-complete healing with marked clinical improvement. During the treatment course, only mild adverse events, including skin dryness and cheilitis, were observed, and no significant laboratory abnormalities occurred. This case suggests that oral acitretin combined with topical 0.1% tretinoin cream may represent a feasible and well-tolerated nonsurgical option for selected elderly patients with facial BCC, and no recurrence was observed during the 4-month follow-up.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":"20 ","pages":"617054"},"PeriodicalIF":4.5,"publicationDate":"2026-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13484617/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148788030","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":"Bovine Milk Exosomes as Natural Cytoprotective Nanoplatforms Against Lead-Induced Toxicity.","authors":"Subhrajita Panda, Faraz Ahmad","doi":"10.2147/BTT.S571251","DOIUrl":"10.2147/BTT.S571251","url":null,"abstract":"<p><strong>Purpose: </strong>Exosomes derived from mammalian milk are extracellular vesicular dietary agents capable of interspecies communication. Bovine milk exosomes (BMEs) are abundant natural nanovesicular resources that are enriched in bioactive components, including proteins, lipids, and microRNAs, and as such possess tremendous potential to affect cellular functions in the consumers. Although the applications of BMEs as delivery platforms for exogenous therapeutics are well known, their endogenous therapeutic potential remains relatively undiscerned. This study aimed to examine the cytoprotective role of BMEs as stand-alone therapeutic agents on human embryonic kidney (HEK293T) cells exposed to a prevalent environmental toxicant, lead (Pb).</p><p><strong>Methods: </strong>Isolation of BMEs was performed using standardized ultracentrifugation-based protocols. The physico-biochemical characterization of BMEs was performed using electron microscopy, Western blotting and dynamic light scattering (DLS). The ameliorative effects of BMEs were evaluated using spectrophotometric assays for cellular viability/toxicity and oxidative stress.</p><p><strong>Results: </strong>Our results confirmed that Pb is a potent cytotoxic chemical, the exposure of which was associated with significant decreases in cellular viabilities in MTT reduction and lactate dehydrogenase (LDH) release assays. Additionally, Pb treatment increased the formation of reactive oxygen (ROS) and nitrogen (RNS) species. However, cotreatment with BMEs significantly mitigated Pb-induced oxidative stress and cellular damage.</p><p><strong>Conclusion: </strong>This study highlights the endogenous potential of BMEs as therapeutic and biotechnological agents against chemical toxicity.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":"20 ","pages":"571251"},"PeriodicalIF":4.5,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13455030/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148705321","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":"Hemophagocytic Lymphohistiocytosis Triggered by HSV‑1 in a Patient with Refractory Crohn's Disease After Long‑Term Sequential Immunosuppressive Therapy.","authors":"Lingya Yao, Hanxiao Tu, Qian Cao","doi":"10.2147/BTT.S616623","DOIUrl":"10.2147/BTT.S616623","url":null,"abstract":"<p><p>Hemophagocytic lymphohistiocytosis (HLH) is a rare syndrome of immune dysregulation. Here, we presented the case of a young male diagnosed with psoriasis and Crohn's disease (CD), after multiple therapy failures, he started upadacitinib (UPA) in 2023. After induction and maintenance therapy, colonoscopy revealed suboptimal disease control. In November 2024, he was admitted to our hospital with fever and elevated liver enzymes, the final diagnosis was HSV-1-associated secondary HLH. After antiviral and hormonal treatment, the patient was discharged in stable condition. This case illustrates that HLH in such patients is rarely attributable to a single drug, rather, it results from the convergence of underlying CD, cumulative multi-agent immunosuppression, and an acute infectious trigger (HSV-1). Clinicians should maintain high vigilance for virus-associated HLH in heavily immunosuppressed IBD patients.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":"20 ","pages":"616623"},"PeriodicalIF":4.5,"publicationDate":"2026-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13431422/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148667987","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":"Safety Profile of Tozorakimab (an Anti-IL-33 Monoclonal Antibody): Data from the FRONTIER Phase 2 Program.","authors":"Rajesh Patel, Dennis Brooks, Elise Gorseth, Rachel Moate, Alexis Hofherr, Chris Kell, Gabriela Luporini Saraiva, Hitesh Pandya, Martin Jenkins, Ioannis Psallidas","doi":"10.2147/BTT.S581444","DOIUrl":"10.2147/BTT.S581444","url":null,"abstract":"<p><strong>Rationale: </strong>Interleukin-33 (IL-33) is a key orchestrator of broad-spectrum downstream host-response mechanisms, including inflammation, tissue homeostasis, and repair. Dysregulation of IL-33 signaling is associated with several pathological conditions. The FRONTIER program comprised four phase 2 signal-finding studies of tozorakimab, an anti-IL-33 human immunoglobulin G1 monoclonal antibody, in diabetic kidney disease (FRONTIER-1), moderate-to-severe atopic dermatitis (FRONTIER-2), moderate-to-severe asthma (FRONTIER-3), and moderate-to-severe chronic obstructive pulmonary disease and chronic bronchitis (FRONTIER-4). This analysis assessed the safety data from these clinical studies.</p><p><strong>Methods: </strong>FRONTIER-1-4 were randomized, double-blind, placebo-controlled studies evaluating the efficacy, safety, pharmacokinetics, and immunogenicity of tozorakimab in adults. Participants received subcutaneous tozorakimab (FRONTIER-1, 30-300 mg; FRONTIER-2, 60-600 mg; FRONTIER-3, 300-600 mg; FRONTIER-4, 600 mg) or placebo every 4 weeks for 4-7 doses, with follow-up periods ranging from 24-36 weeks from the first dose. Safety (adverse events [AEs], serious AEs, and AEs of special interest) and immunogenicity endpoints from the FRONTIER studies were summarized.</p><p><strong>Results: </strong>In total, 1076 patients were included in this analysis (tozorakimab, n=738; placebo, n=338). Deaths occurred only in FRONTIER-1, in similar proportions between treatment groups (tozorakimab, 0.9%; placebo, 0.8%), and were unrelated to tozorakimab. The proportion of participants experiencing at least one treatment-emergent AE (TEAE) or serious TEAEs was generally similar between tozorakimab and placebo groups. The proportion of participants experiencing AEs of special interest, including events of progression of heart failure, was low (tozorakimab, 0.0-1.5%; placebo, 0.0-0.8%), with no meaningful differences between groups; the frequency of injection-site reactions was however higher in tozorakimab than in placebo recipients (tozorakimab, 1.2-20.9%; placebo, 0.0-4.9%). No clinically significant trends were observed in laboratory or vital-sign parameters, and immunogenicity was low.</p><p><strong>Conclusion: </strong>Tozorakimab was well tolerated across a range of inflammatory diseases, with no safety concerns identified.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":"20 ","pages":"581444"},"PeriodicalIF":4.5,"publicationDate":"2026-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13426366/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148652870","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":"Vunakizumab for IL-17A-Mediated Diseases: A Review in Psoriasis and Spondyloarthritis.","authors":"Hongzhuo Yan, Yu Chen, Yali Song, Min Yan, Kexiang Yan","doi":"10.2147/BTT.S500475","DOIUrl":"10.2147/BTT.S500475","url":null,"abstract":"<p><p>The interleukin-17A (IL-17A) cytokine is a key driver in the pathogenesis of chronic immune-mediated diseases, including psoriasis (PsO), psoriatic arthritis (PsA), and ankylosing spondylitis (AS). As a central proinflammatory mediator, IL-17A signals through the IL-17RA/RC receptor complex to promote tissue-specific inflammation. This narrative review outlines the therapeutic rationale for targeting IL-17A and summarizes the current evidence for vunakizumab, a novel humanized monoclonal antibody against IL-17A. We reviewed the biological basis of IL-17A signaling and its pathogenic role in PsO, PsA, and AS. We then synthesized the pharmacokinetic properties of vunakizumab and the clinical evidence from Phase II and III trials evaluating its efficacy and safety. Post hoc analyses across a broad range of clinically relevant patient subgroups further support the consistency of its therapeutic effects. Clinical trial data demonstrate that vunakizumab offers robust efficacy and a favorable safety profile in the treatment of psoriasis and spondyloarthritis (including PsA and AS). Its properties are comparable to other approved IL-17A inhibitors, establishing it as a promising therapeutic option for these IL-17A-mediated diseases.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":"20 ","pages":"500475"},"PeriodicalIF":4.5,"publicationDate":"2026-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13262571/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148248963","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":"Immunological Biomarkers in Glioblastoma: Targeting T and NK Cells for Enhanced Diagnosis and Prognosis.","authors":"Amir Mohammad Akbari, Shahriyar Bourbour, Maryam Sadat Seyedmehdi, Sara Shiari, Auob Rustamzadeh, Farhad Seif, Shirin Farivar","doi":"10.2147/BTT.S603545","DOIUrl":"10.2147/BTT.S603545","url":null,"abstract":"<p><p>Glioblastoma (GBM) is an aggressive brain tumor with a poor prognosis, even with many therapeutic interventions, including surgery, chemotherapy, and radiotherapy. Recent immunotherapies have broaden horizons to the utilization of the immune system to eradicate GBM. However, the clinical efficacy of such approaches is limited, owing to the tumor's multifaceted immunosuppressive microenvironment and the blood-brain barrier (BBB) structure. The dysfunction of immune cells, especially T cells and natural killer (NK) cells, is significantly influenced by the immunosuppressive mechanisms in GBM. Novel therapeutic strategies are needed to overcome these mechanisms. In the current review, we explore the main functions of T cells, especially cytotoxic CD4⁺ and helper CD8⁺ T cells, alongside NK cells, in response to GBM. We further discuss the mechanisms contributing to their dysfunction, focusing on T cell exhaustion, altered receptor expression, and metabolic reprogramming within the GBM microenvironment to establish diagnostic and prognostic biomarkers. Moreover, we highlight recent advances in immunotherapeutic approaches, including immune checkpoint inhibitors (ICI), miRNA therapy, oncolytic viruses, and Chimeric Antigen Receptor (CAR) T/NK cell therapy to provide new opportunities for enhancing GBM treatment and biomarker-guided precision medicine.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":"20 ","pages":"603545"},"PeriodicalIF":4.5,"publicationDate":"2026-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13228866/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148154936","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":"MicroRNA-661 Suppresses Proliferation and Migration of Pulmonary Artery Smooth Muscle Cells and Endothelial Cells by Targeting CCND2.","authors":"Liyang Jiang, Aixiang Yang, Jun Liu, Jie Zhou","doi":"10.2147/BTT.S592879","DOIUrl":"10.2147/BTT.S592879","url":null,"abstract":"<p><strong>Introduction: </strong>Pulmonary arterial hypertension (PAH) is a fatal cardiovascular disorder driven by pulmonary vascular remodeling, with high morbidity and mortality. Current therapies only alleviate symptoms and cannot reverse disease progression. Our previous study has demonstrated that microRNA-661 (miR-661) inhibits Human pulmonary artery smooth muscle cell (HPASMC) and Human pulmonary artery endothelial cell (HPAEC) proliferation, but its underlying molecular mechanism in PAH remains unclear. This study aimed to identify the target gene of miR-661 and elucidate its regulatory role in PAH pathogenesis, seeking novel therapeutic targets for this incurable disease.</p><p><strong>Methods: </strong>Serum samples from 12 PAH patients and 12 healthy volunteers were enrolled this research. Human pulmonary artery smooth muscle cells (HPASMCs) and endothelial cells (HPAECs) were cultured under normoxic or hypoxic conditions. MiR-661 mimics/inhibitors and CCND2 plasmids were transfected into cells. RNA-seq screened differentially expressed genes, and dual-luciferase reporter assay verified the target binding of miR-661. RT-qPCR and Western blot detected gene/protein expression, while MTT, EdU, Transwell and flow cytometry assessed cell proliferation, migration and cycle progression.</p><p><strong>Results: </strong>We perform RNA-seq and luciferase assay and found that CCND2 is a direct miR-661 target that is repressed via 3'UTR binding. miR-661 is lower expressed while the expression of CCND2 is higher in PAH patient serum and hypoxic HPASMCs/HPAECs, showing a significant negative correlation. CCND2 overexpression promoted pulmonary artery cell cycle progression, proliferation and migration under hypoxia, while miR-661 overexpression reversed these effects. In addition, we found that Stattic, a specific inhibitor of STAT3 (an upstream regulatory protein of CCND2), could inhibit HPASMC cell proliferation and migration and this effect is enhanced by miR-661.</p><p><strong>Discussion: </strong>This study clarifies that miR-661 suppresses HPASMC and HPAEC proliferation or migration by targeting CCND2, and the miR-661/CCND2 axis is a key regulatory pathway in PAH-related vascular remodeling. Hypoxia-induced miR-661 downregulation leads to CCND2 accumulation, driving abnormal pulmonary artery cell biological behaviors. miR-661/CCND2 axis regulates PAH progression, providing a potential therapeutic target.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":"20 ","pages":"592879"},"PeriodicalIF":4.5,"publicationDate":"2026-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13225285/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148148252","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}