Pub Date : 2026-01-26DOI: 10.1016/j.bbrc.2026.153350
Hong Zhang, Chengcheng Pei, Chenglin Huang, Hui Luo, Zhuona Zheng, Ci Zhang, Ming Zhang
Objective: This study aims to evaluate the potential of LINC00494 in the diagnosis of osteoporotic fractures (OPF) and to explore its potential molecular mechanisms in fracture healing.
Methods: The expression of LINC00494, miR-185-3p, runt-related transcription factor 2 (RUNX2), alkaline phosphatase (ALP), osteocalcin (OCN), and Collagen I were measured using reverse transcription quantitative polymerase chain reaction (RT-qPCR). The diagnostic value of LINC00494 for OPF and delayed healing was assessed by receiver operating characteristic (ROC) curves. A dual luciferase reporter (DLR) assay was employed to validate the targeting interaction between LINC00494 and miR-185-3p. The proliferation of human bone marrow mesenchymal stem cells (HBMSCs) was detected using a Cell Counting Kit-8 (CCK-8) assay, and apoptosis was assessed by flow cytometry.
Results: LINC00494 expression was significantly downregulated in patients with OPF and delayed fracture healing (DFH) and demonstrated a strong predictive ability. Multivariate regression analysis indicated that LINC00494 is an independent predictor of DFH. Functional experiments revealed that LINC00494 upregulates the expression of key osteogenic markers, promotes the proliferation of HBMSCs, and inhibits apoptosis. However, overexpression of miR-185-3p reversed the promotive effects of LINC00494 on osteogenic differentiation and its inhibitory effect on apoptosis.
Conclusion: LINC00494 demonstrates potential as a diagnostic biomarker for OPF and DFH, and promotes the fracture healing process by binding to miR-185-3p.
{"title":"The value of LINC00494 aberrant expression in the diagnosis and promotion of fracture healing in patients with osteoporotic fractures.","authors":"Hong Zhang, Chengcheng Pei, Chenglin Huang, Hui Luo, Zhuona Zheng, Ci Zhang, Ming Zhang","doi":"10.1016/j.bbrc.2026.153350","DOIUrl":"https://doi.org/10.1016/j.bbrc.2026.153350","url":null,"abstract":"<p><strong>Objective: </strong>This study aims to evaluate the potential of LINC00494 in the diagnosis of osteoporotic fractures (OPF) and to explore its potential molecular mechanisms in fracture healing.</p><p><strong>Methods: </strong>The expression of LINC00494, miR-185-3p, runt-related transcription factor 2 (RUNX2), alkaline phosphatase (ALP), osteocalcin (OCN), and Collagen I were measured using reverse transcription quantitative polymerase chain reaction (RT-qPCR). The diagnostic value of LINC00494 for OPF and delayed healing was assessed by receiver operating characteristic (ROC) curves. A dual luciferase reporter (DLR) assay was employed to validate the targeting interaction between LINC00494 and miR-185-3p. The proliferation of human bone marrow mesenchymal stem cells (HBMSCs) was detected using a Cell Counting Kit-8 (CCK-8) assay, and apoptosis was assessed by flow cytometry.</p><p><strong>Results: </strong>LINC00494 expression was significantly downregulated in patients with OPF and delayed fracture healing (DFH) and demonstrated a strong predictive ability. Multivariate regression analysis indicated that LINC00494 is an independent predictor of DFH. Functional experiments revealed that LINC00494 upregulates the expression of key osteogenic markers, promotes the proliferation of HBMSCs, and inhibits apoptosis. However, overexpression of miR-185-3p reversed the promotive effects of LINC00494 on osteogenic differentiation and its inhibitory effect on apoptosis.</p><p><strong>Conclusion: </strong>LINC00494 demonstrates potential as a diagnostic biomarker for OPF and DFH, and promotes the fracture healing process by binding to miR-185-3p.</p>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"806 ","pages":"153350"},"PeriodicalIF":2.2,"publicationDate":"2026-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146140789","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Diabetic kidney disease (DKD) is a leading cause of end-stage renal disease, driven by hyperglycemia-induced mitochondrial apoptosis in renal tubular epithelial cells. Death-associated protein kinase 1 (DAPK1) is a key mediator of cell death, but its regulation in DKD remains unclear. Here, we investigated the mechanisms underlying DAPK1 upregulation and its role in mitochondrial apoptosis under high glucose (HG) conditions in HK-2 cells and db/db mouse models. In db/db mice, renal DAPK1 protein levels were elevated, while KLHL20 levels were reduced, correlating with glomerular and tubular injury. In HK-2 cells, HG (33 mM, 48 h) significantly increased DAPK1 mRNA and protein levels while prolonging its half-life. Mechanistically, HG transcriptionally suppressed KLHL20, an E3 ubiquitin ligase adaptor that targets DAPK1 for proteasomal degradation. Co-immunoprecipitation confirmed KLHL20-DAPK1 interaction and showed reduced DAPK1 ubiquitination under HG. Overexpression of KLHL20 restored DAPK1 ubiquitination and reduced its protein levels without affecting mRNA, confirming post-translational regulation. Functionally, DAPK1 knockdown attenuated HG-induced mitochondrial apoptosis. KLHL20 overexpression similarly protected against HG-induced apoptosis, but this effect was abrogated by DAPK1 co-overexpression, establishing DAPK1 as a critical downstream effector. These findings reveal a novel KLHL20-DAPK1 axis where HG stabilizes DAPK1 by downregulating KLHL20, promoting mitochondrial apoptosis in renal tubular cells. Targeting this pathway may offer therapeutic strategies for DKD.
糖尿病肾病（DKD）是终末期肾脏疾病的主要原因，由高血糖诱导的肾小管上皮细胞线粒体凋亡驱动。死亡相关蛋白激酶1 （DAPK1）是细胞死亡的关键介质，但其在DKD中的调控尚不清楚。在此，我们在HK-2 细胞和db/db小鼠模型中研究了高糖（HG）条件下DAPK1上调的机制及其在线粒体凋亡中的作用。在db/db小鼠中，肾脏DAPK1蛋白水平升高，而KLHL20水平降低，与肾小球和小管损伤相关。在HK-2 细胞中，HG（33 mM, 48 h）显著提高了DAPK1 mRNA和蛋白水平，延长了其半衰期。在机制上，HG转录抑制了KLHL20，这是一种E3泛素连接酶适配器，靶向DAPK1进行蛋白酶体降解。共免疫沉淀证实了KLHL20-DAPK1相互作用，并显示HG下DAPK1泛素化降低。过表达KLHL20恢复了DAPK1泛素化，降低了其蛋白水平，但不影响mRNA，证实了翻译后调控。功能上，DAPK1敲低可减弱hg诱导的线粒体凋亡。KLHL20过表达同样可以防止hg诱导的细胞凋亡，但这种作用被DAPK1共过表达所消除，这表明DAPK1是一个关键的下游效应物。这些发现揭示了一个新的KLHL20-DAPK1轴，HG通过下调KLHL20来稳定DAPK1，促进肾小管细胞线粒体凋亡。靶向这一途径可能为DKD提供治疗策略。
{"title":"KLHL20 alleviates high glucose-induced mitochondrial apoptosis in renal tubular cells by targeting DAPK1 for ubiquitination and degradation.","authors":"Yi Lei, Chenlin Gao, Xin Zhao, Betty Yuen Kwan Law, Yong Xu","doi":"10.1016/j.bbrc.2026.153345","DOIUrl":"https://doi.org/10.1016/j.bbrc.2026.153345","url":null,"abstract":"<p><p>Diabetic kidney disease (DKD) is a leading cause of end-stage renal disease, driven by hyperglycemia-induced mitochondrial apoptosis in renal tubular epithelial cells. Death-associated protein kinase 1 (DAPK1) is a key mediator of cell death, but its regulation in DKD remains unclear. Here, we investigated the mechanisms underlying DAPK1 upregulation and its role in mitochondrial apoptosis under high glucose (HG) conditions in HK-2 cells and db/db mouse models. In db/db mice, renal DAPK1 protein levels were elevated, while KLHL20 levels were reduced, correlating with glomerular and tubular injury. In HK-2 cells, HG (33 mM, 48 h) significantly increased DAPK1 mRNA and protein levels while prolonging its half-life. Mechanistically, HG transcriptionally suppressed KLHL20, an E3 ubiquitin ligase adaptor that targets DAPK1 for proteasomal degradation. Co-immunoprecipitation confirmed KLHL20-DAPK1 interaction and showed reduced DAPK1 ubiquitination under HG. Overexpression of KLHL20 restored DAPK1 ubiquitination and reduced its protein levels without affecting mRNA, confirming post-translational regulation. Functionally, DAPK1 knockdown attenuated HG-induced mitochondrial apoptosis. KLHL20 overexpression similarly protected against HG-induced apoptosis, but this effect was abrogated by DAPK1 co-overexpression, establishing DAPK1 as a critical downstream effector. These findings reveal a novel KLHL20-DAPK1 axis where HG stabilizes DAPK1 by downregulating KLHL20, promoting mitochondrial apoptosis in renal tubular cells. Targeting this pathway may offer therapeutic strategies for DKD.</p>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"805 ","pages":"153345"},"PeriodicalIF":2.2,"publicationDate":"2026-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146117575","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-25DOI: 10.1016/j.bbrc.2026.153334
Tianhui Chao , Xiaoyu Fu , Hongyu Sun , Xianzhen Yin , Sha Xu , Ruifang Gao , Guodong Chen , Yang Zhao , Shilin Zhou , Xiaoliang Li , Xiaoxu Hao , Tingting Li , Yunpeng Zhao , Yue Wang
Technical limitations hinder the clinical translation of exosomes for precise visualization of their in vivo pharmacokinetics. Conventional fluorescent labelling methods suffer from low signal-to-noise ratios, which hamper three-dimensional (3D), high-resolution, and quantitative analysis of exosome distribution at the whole-organ scale. To address this challenge, this study established an integrated “fluorescent mRNA labelling-fMOST imaging” technology system. Exosomes were labelled with fluorescent mRNA; in vitro characterization confirmed that the nucleic acid tags were efficiently loaded into exosomes without compromising their structural integrity, while demonstrating significantly superior signal-to-noise ratios and stability over traditional DiO dyes. Using light-sheet microscopy and quantitative analysis, we compared the pulmonary distribution of exosomes across different administration routes. The results indicated that lung accumulation following tail-vein injection was 2.48-fold higher than that of intranasal administration. Furthermore, fluorescence Micro-Optical Sectioning Tomography (fMOST) imaging provided a high-resolution 3D map of exosomes throughout the entire lung. The technology platform established in this study achieves single-exosome spatial resolution of in vivo distribution, offering key methodological tools and data support for evaluating the targeting efficiency of exosomal drugs and optimising delivery strategies, thereby facilitating their clinical translation.
{"title":"High-resolution imaging of exosome pulmonary spatial distribution via fluorescent mRNA labeling and fMOST","authors":"Tianhui Chao , Xiaoyu Fu , Hongyu Sun , Xianzhen Yin , Sha Xu , Ruifang Gao , Guodong Chen , Yang Zhao , Shilin Zhou , Xiaoliang Li , Xiaoxu Hao , Tingting Li , Yunpeng Zhao , Yue Wang","doi":"10.1016/j.bbrc.2026.153334","DOIUrl":"10.1016/j.bbrc.2026.153334","url":null,"abstract":"<div><div>Technical limitations hinder the clinical translation of exosomes for precise visualization of their in vivo pharmacokinetics. Conventional fluorescent labelling methods suffer from low signal-to-noise ratios, which hamper three-dimensional (3D), high-resolution, and quantitative analysis of exosome distribution at the whole-organ scale. To address this challenge, this study established an integrated “fluorescent mRNA labelling-fMOST imaging” technology system. Exosomes were labelled with fluorescent mRNA; in vitro characterization confirmed that the nucleic acid tags were efficiently loaded into exosomes without compromising their structural integrity, while demonstrating significantly superior signal-to-noise ratios and stability over traditional DiO dyes. Using light-sheet microscopy and quantitative analysis, we compared the pulmonary distribution of exosomes across different administration routes. The results indicated that lung accumulation following tail-vein injection was 2.48-fold higher than that of intranasal administration. Furthermore, fluorescence Micro-Optical Sectioning Tomography (fMOST) imaging provided a high-resolution 3D map of exosomes throughout the entire lung. The technology platform established in this study achieves single-exosome spatial resolution of in vivo distribution, offering key methodological tools and data support for evaluating the targeting efficiency of exosomal drugs and optimising delivery strategies, thereby facilitating their clinical translation.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"803 ","pages":"Article 153334"},"PeriodicalIF":2.2,"publicationDate":"2026-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146076719","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chemical investigation of a mangrove-associated Aspergillus strain GXNU-31G, cultivated under saline fermentation conditions, yielded a new sesquiterpenoid named guxinusocapsa B (1) together with four congeners. Its planar framework and absolute stereochemistry were established through comprehensive analysis of 1D/2D NMR spectra, HR-ESI-MS data, and single-crystal X-ray crystallography. Bioassays of compounds 1–4 against the Asian citrus psyllid (Diaphorina citri) revealed that the newly characterized metabolite 1 elicited potent lethality, causing 95 % mortality at a dosage of 1000 mg kg−1.
{"title":"A new sesquiterpenoid from the Fungus Aspergillus sp. and its insecticidal activity","authors":"Ping Wu , Yonghua Wu , Yaming Chen , Xianglong Bo , Jinwei Chen , Xishan Huang , Jiguo Huang , Xiongtao Yu","doi":"10.1016/j.bbrc.2026.153335","DOIUrl":"10.1016/j.bbrc.2026.153335","url":null,"abstract":"<div><div>Chemical investigation of a mangrove-associated <em>Aspergillus</em> strain GXNU-31G, cultivated under saline fermentation conditions, yielded a new sesquiterpenoid named guxinusocapsa B (<strong>1</strong>) together with four congeners. Its planar framework and absolute stereochemistry were established through comprehensive analysis of 1D/2D NMR spectra, HR-ESI-MS data, and single-crystal X-ray crystallography. Bioassays of compounds <strong>1</strong>–<strong>4</strong> against the Asian citrus psyllid (<em>Diaphorina citri</em>) revealed that the newly characterized metabolite <strong>1</strong> elicited potent lethality, causing 95 % mortality at a dosage of 1000 mg kg<sup>−1</sup>.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"802 ","pages":"Article 153335"},"PeriodicalIF":2.2,"publicationDate":"2026-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146050255","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-24DOI: 10.1016/j.bbrc.2026.153347
Qianwen Zhu , Wenhao Gu , Yuyang Lv , Zizhao Wu , Yan Li , Rongxin Zhang , Xianli Shi
Crohn's disease (CD) is a chronic inflammatory condition of the gastrointestinal tract characterized by symptoms such as abdominal pain, diarrhea, weight loss, fever, and fatigue. Although the exact etiology of CD remains elusive, dysregulation of immune cells is widely recognized as a primary driver in its pathogenesis, particularly involving T helper 1 (Th1), T helper 17 (Th17), and natural killer T (NKT) cells. Recent advancements in single-cell sequencing technology have provided a powerful tool for analyzing gene expression at the individual cell level, enabling researchers to investigate immune cells within the microenvironment of disease samples with unprecedented resolution. Through the application of this technology, several novel and unique immune cell subsets have been identified in Crohn's disease, which are critical to its development and progression. This review summarizes these CD-associated cell types, including INFLAREs, LND cells, Tc1/17 cells, tissue-resident memory (Trm) CD8+ T cells, FOXP3+ regulatory T cells (Tregs), CD pop cells, α4β7+CLA+ T cells, NKp30+ γδ T cells, and Crohn's disease-associated invariant T cells (CAITs). We discuss their specific roles in the pathogenesis of CD and explore their potential as targets for the development of future therapeutic interventions. Thereby, this may serve as a conceptual and practical resource for researchers and clinicians seeking to understand the immunological intricacies of CD and translate them into improved patient outcomes in the future.
{"title":"Crohn's disease under single-cell map: from INFLARE metaplastic cells to rare immune cell subpopulations","authors":"Qianwen Zhu , Wenhao Gu , Yuyang Lv , Zizhao Wu , Yan Li , Rongxin Zhang , Xianli Shi","doi":"10.1016/j.bbrc.2026.153347","DOIUrl":"10.1016/j.bbrc.2026.153347","url":null,"abstract":"<div><div>Crohn's disease (CD) is a chronic inflammatory condition of the gastrointestinal tract characterized by symptoms such as abdominal pain, diarrhea, weight loss, fever, and fatigue. Although the exact etiology of CD remains elusive, dysregulation of immune cells is widely recognized as a primary driver in its pathogenesis, particularly involving T helper 1 (Th1), T helper 17 (Th17), and natural killer T (NKT) cells. Recent advancements in single-cell sequencing technology have provided a powerful tool for analyzing gene expression at the individual cell level, enabling researchers to investigate immune cells within the microenvironment of disease samples with unprecedented resolution. Through the application of this technology, several novel and unique immune cell subsets have been identified in Crohn's disease, which are critical to its development and progression. This review summarizes these CD-associated cell types, including INFLAREs, LND cells, Tc1/17 cells, tissue-resident memory (Trm) CD8<sup>+</sup> T cells, FOXP3<sup>+</sup> regulatory T cells (Tregs), CD pop cells, α<sup>4</sup>β<sup>7+</sup>CLA<sup>+</sup> T cells, NKp30<sup>+</sup> γδ T cells, and Crohn's disease-associated invariant T cells (CAITs). We discuss their specific roles in the pathogenesis of CD and explore their potential as targets for the development of future therapeutic interventions. Thereby, this may serve as a conceptual and practical resource for researchers and clinicians seeking to understand the immunological intricacies of CD and translate them into improved patient outcomes in the future.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"803 ","pages":"Article 153347"},"PeriodicalIF":2.2,"publicationDate":"2026-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146076674","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-24DOI: 10.1016/j.bbrc.2026.153349
Agrima Sharma, Ritu Kulshreshtha, Shyam S Chauhan, Rafat Malik, Vaishali Suri, Amandeep Jagdevan, Mehar Chand Sharma
<p><strong>Background: </strong>Supratentorial ependymomas frequently harbor ZFTA-RELA (ZRfus) gene fusions that initiate oncogenic transcriptional programs; however, the downstream post-transcriptional regulatory mechanisms remain poorly understood. This study aimed to elucidate the contribution of microRNAs (miRNAs) to the aggressive phenotype characteristic of ZRfus <sup>+</sup> tumors.</p><p><strong>Methods: </strong>Small RNA sequencing was performed on fusion-positive (ZRfus<sup>+</sup>) and fusion-negative (ZRfus<sup>-</sup>) supratentorial ependymomas, followed by integrative bioinformatic analyses. Differentially expressed miRNAs and their predicted mRNA targets were validated using quantitative real-time PCR (qRT-PCR) and immunohistochemistry (IHC). Associations with clinical outcomes were evaluated through progression-free survival (PFS) analysis.</p><p><strong>Results: </strong>Distinct miRNA expression profiles discriminated ZRfus<sup>+</sup> from ZRfus<sup>-</sup> tumors. ZRfus <sup>+</sup> tumors demonstrated significant upregulation of hsa-miR-138-5p and downregulation of hsa-miR-135b-5p and hsa-miR-216a-3p. Target prediction and pathway enrichment analyses identified TERT, YAP1, RELA, and TP53 as key dysregulated network nodes. Functionally, ZRfus<sup>+</sup> tumors exhibited enhanced epithelial-mesenchymal transition (EMT) and stemness signatures, marked by upregulation of SNAIL, SLUG, Nestin, and N-Cadherin. Clinically, ZRfus <sup>+</sup> status correlated with significantly shorter progression-free survival, underscoring its adverse prognostic significance.</p><p><strong>Conclusions: </strong>This study delineates a distinct ZR fus-associated miRNA landscape in supratentorial ependymomas, implicates hsa-miR-138-5p as a potential biomarker of oncogenic signaling and EMT activation, and reveals mechanistic links between fusion-driven transcriptional dysregulation and tumor aggressiveness. These findings lay the groundwork for miRNA-based therapeutic strategies in high-risk pediatric ependymoma subtypes.</p><p><strong>Importance of the study: </strong>Supratentorial ependymomas with ZFTA-RELA fusions represent a highly aggressive pediatric brain tumor subtype, yet the post-transcriptional mechanisms driving their malignancy remain unclear. This study fills a critical gap by systematically profiling miRNA expression in fusion-positive and fusion-negative supratentorial ependymomas, revealing a distinct fusion-associated miRNA signature. The identification of hsa-miR-138-5p upregulation and hsa-miR-135b-5p/hsa-miR-216a-3p downregulation, converging on key oncogenic nodes such as TERT, YAP1, RELA, and TP53, provides novel mechanistic insight into how fusion-driven miRNA dysregulation enhances epithelial-mesenchymal transition and stemness. The findings suggest that miRNA-fusion interactions play an important role in tumor aggressiveness and highlight hsa-miR-138-5p as a potential biomarker for disease progression. Clinically, the wo
{"title":"Unraveling the miRNA-EMT-stemness interplay in fusion-positive supratentorial ependymomas: Identifying therapeutic vulnerabilities.","authors":"Agrima Sharma, Ritu Kulshreshtha, Shyam S Chauhan, Rafat Malik, Vaishali Suri, Amandeep Jagdevan, Mehar Chand Sharma","doi":"10.1016/j.bbrc.2026.153349","DOIUrl":"https://doi.org/10.1016/j.bbrc.2026.153349","url":null,"abstract":"<p><strong>Background: </strong>Supratentorial ependymomas frequently harbor ZFTA-RELA (ZRfus) gene fusions that initiate oncogenic transcriptional programs; however, the downstream post-transcriptional regulatory mechanisms remain poorly understood. This study aimed to elucidate the contribution of microRNAs (miRNAs) to the aggressive phenotype characteristic of ZRfus <sup>+</sup> tumors.</p><p><strong>Methods: </strong>Small RNA sequencing was performed on fusion-positive (ZRfus<sup>+</sup>) and fusion-negative (ZRfus<sup>-</sup>) supratentorial ependymomas, followed by integrative bioinformatic analyses. Differentially expressed miRNAs and their predicted mRNA targets were validated using quantitative real-time PCR (qRT-PCR) and immunohistochemistry (IHC). Associations with clinical outcomes were evaluated through progression-free survival (PFS) analysis.</p><p><strong>Results: </strong>Distinct miRNA expression profiles discriminated ZRfus<sup>+</sup> from ZRfus<sup>-</sup> tumors. ZRfus <sup>+</sup> tumors demonstrated significant upregulation of hsa-miR-138-5p and downregulation of hsa-miR-135b-5p and hsa-miR-216a-3p. Target prediction and pathway enrichment analyses identified TERT, YAP1, RELA, and TP53 as key dysregulated network nodes. Functionally, ZRfus<sup>+</sup> tumors exhibited enhanced epithelial-mesenchymal transition (EMT) and stemness signatures, marked by upregulation of SNAIL, SLUG, Nestin, and N-Cadherin. Clinically, ZRfus <sup>+</sup> status correlated with significantly shorter progression-free survival, underscoring its adverse prognostic significance.</p><p><strong>Conclusions: </strong>This study delineates a distinct ZR fus-associated miRNA landscape in supratentorial ependymomas, implicates hsa-miR-138-5p as a potential biomarker of oncogenic signaling and EMT activation, and reveals mechanistic links between fusion-driven transcriptional dysregulation and tumor aggressiveness. These findings lay the groundwork for miRNA-based therapeutic strategies in high-risk pediatric ependymoma subtypes.</p><p><strong>Importance of the study: </strong>Supratentorial ependymomas with ZFTA-RELA fusions represent a highly aggressive pediatric brain tumor subtype, yet the post-transcriptional mechanisms driving their malignancy remain unclear. This study fills a critical gap by systematically profiling miRNA expression in fusion-positive and fusion-negative supratentorial ependymomas, revealing a distinct fusion-associated miRNA signature. The identification of hsa-miR-138-5p upregulation and hsa-miR-135b-5p/hsa-miR-216a-3p downregulation, converging on key oncogenic nodes such as TERT, YAP1, RELA, and TP53, provides novel mechanistic insight into how fusion-driven miRNA dysregulation enhances epithelial-mesenchymal transition and stemness. The findings suggest that miRNA-fusion interactions play an important role in tumor aggressiveness and highlight hsa-miR-138-5p as a potential biomarker for disease progression. Clinically, the wo","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"804 ","pages":"153349"},"PeriodicalIF":2.2,"publicationDate":"2026-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146103456","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-23DOI: 10.1016/j.bbrc.2026.153329
Yong Zhao, Jia Luo, Lu Wu
Diabetes-induced testicular damage (DITD) is a common complication of diabetes mellitus (DM), impairing spermatogenesis and contributing to male infertility, a condition associated with polypeptide N-acetylgalactoacyltransferase 3 (GALNT3), a critical enzyme for protein glycosylation. However, the role of GALNT3 in DITD progression remains elusive. This study elucidated the action of GALNT3 on DITD pathogenesis and investigated the potential underlying mechanism. Mouse spermatogenic GC-1 spg cells were stimulated by high glucose (HG) to establish the in vitro model of DITD. Cell viability and apoptosis were evaluated utilizing the CCK-8 method and flow cytometry, respectively. Reactive oxygen species (ROS) production and mitochondrial membrane potential (MMP) levels were measured utilizing flow cytometry. Coimmunoprecipitation was performed to measure the binding of GALNT3 to AKT1. The GalNAc-type O-glycosylation of AKT1 was defined utilizing the lectin pull-down assay. The ChIP-PCR and dual-luciferase reporter assays were performed to determine the binding of cAMP response element-binding (CREB) to the GLANT3 promoter. GLANT3 expression was reduced in HG-induced GC-1 spg cells. Overexpressed Glant3 restrained HG-stimulated apoptosis and ROS production and elevated the HG-induced decrease of the MMP levels of GC-1 spg cells. Besides, AKT1 signaling pathway inactivation mediated the induction of silenced Glant3 on apoptosis and mitochondrial dysfunction. Further investigation found that GLANT3 induced AKT1 glycosylation to suppress HG-induced apoptosis and mitochondrial dysfunction. Moreover, transcription factor CREB could bind to the Glant3 promoter and regulate promoter activity. GALNT3-mediated AKT1 glycosylation activated the AKT1/CREB signaling pathway to inhibit HG-induced spermatogenic cell apoptosis and mitochondrial dysfunction. Therefore, GLANT3 might be a valuable target for DITD management.
{"title":"GALNT3-mediated AKT1 glycosylation activates the AKT1/CREB signaling pathway to inhibit high glucose-induced spermatogenic cell apoptosis and mitochondrial dysfunction","authors":"Yong Zhao, Jia Luo, Lu Wu","doi":"10.1016/j.bbrc.2026.153329","DOIUrl":"10.1016/j.bbrc.2026.153329","url":null,"abstract":"<div><div>Diabetes-induced testicular damage (DITD) is a common complication of diabetes mellitus (DM), impairing spermatogenesis and contributing to male infertility, a condition associated with polypeptide N-acetylgalactoacyltransferase 3 (GALNT3), a critical enzyme for protein glycosylation. However, the role of GALNT3 in DITD progression remains elusive. This study elucidated the action of GALNT3 on DITD pathogenesis and investigated the potential underlying mechanism. Mouse spermatogenic GC-1 spg cells were stimulated by high glucose (HG) to establish <em>the in vitro</em> model of DITD. Cell viability and apoptosis were evaluated utilizing the CCK-8 method and flow cytometry, respectively. Reactive oxygen species (ROS) production and mitochondrial membrane potential (MMP) levels were measured utilizing flow cytometry. Coimmunoprecipitation was performed to measure the binding of GALNT3 to AKT1. The GalNAc-type O-glycosylation of AKT1 was defined utilizing the lectin pull-down assay. The ChIP-PCR and dual-luciferase reporter assays were performed to determine the binding of cAMP response element-binding (CREB) to the GLANT3 promoter. GLANT3 expression was reduced in HG-induced GC-1 spg cells. Overexpressed <em>Glant3</em> restrained HG-stimulated apoptosis and ROS production and elevated the HG-induced decrease of the MMP levels of GC-1 spg cells. Besides, AKT1 signaling pathway inactivation mediated the induction of silenced <em>Glant3</em> on apoptosis and mitochondrial dysfunction. Further investigation found that GLANT3 induced AKT1 glycosylation to suppress HG-induced apoptosis and mitochondrial dysfunction. Moreover, transcription factor CREB could bind to the <em>Glant3</em> promoter and regulate promoter activity. GALNT3-mediated AKT1 glycosylation activated the AKT1/CREB signaling pathway to inhibit HG-induced spermatogenic cell apoptosis and mitochondrial dysfunction. Therefore, GLANT3 might be a valuable target for DITD management.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"802 ","pages":"Article 153329"},"PeriodicalIF":2.2,"publicationDate":"2026-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146059198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The SARS-CoV-2 pandemic supercharged global efforts towards cutting-edge vaccination strategies for current threats and emerging viruses. It is imperative to develop and investigate next-generation vaccines such as chimeric Virus-Like Particles (chi-VLPs) vaccines for increased immunogenicity, ease of production, and scalability to supplement the worldwide vaccine supply. This study reports a novel bivalent vaccine design of Chimeric Alphavirus-Coronavirus Virus-Like Particles (ChAC-VLPs), displaying fusion glycoproteins of Chikungunya virus (CHIKV) and a Receptor Binding Domain (RBD) of SARS-CoV-2 on its surface. The uniqueness and versatility of ChAC-VLPs have been demonstrated via various techniques, including Western blot, Immunofluorescence, cryo-EM, and Dynamic Light Scattering (DLS). The multimeric epitope display of immunogenic antigens was validated by cell-based assays. ChAC-VLP immunized mice sera have shown substantial neutralization titers for CHIKV (PRNT50 of 1:25). Similarly, serum antibodies were detected for SARS-CoV-2 RBD as observed by antigen-specific ELISA and validated using Surface Plasmon Resonance (SPR). ChAC-VLP-immunized mice sera at a 1:10 dilution exhibited 80-95 % SARS-CoV-2 pseudovirus neutralization relative to the untreated virus control. In conclusion, this study proposes ChAC-VLPs as a potential hybrid vaccine candidate for CHIKV and SARS-CoV-2 infections and contributes valuable insights into the chi-VLPs domain and its design.
{"title":"Bioengineered chimeric VLPs targeting chikungunya virus and SARS-CoV-2 show high immunogenicity in mice.","authors":"Vedita Anand Singh, Sanketkumar Nehul, Ankita Saha, Vishakha Singh, Mandar Bhutkar, Chandra Shekhar Kumar, Manidipa Banerjee, Richard J Kuhn, Pravindra Kumar, Gaurav Kumar Sharma, Shailly Tomar","doi":"10.1016/j.bbrc.2026.153346","DOIUrl":"https://doi.org/10.1016/j.bbrc.2026.153346","url":null,"abstract":"<p><p>The SARS-CoV-2 pandemic supercharged global efforts towards cutting-edge vaccination strategies for current threats and emerging viruses. It is imperative to develop and investigate next-generation vaccines such as chimeric Virus-Like Particles (chi-VLPs) vaccines for increased immunogenicity, ease of production, and scalability to supplement the worldwide vaccine supply. This study reports a novel bivalent vaccine design of Chimeric Alphavirus-Coronavirus Virus-Like Particles (ChAC-VLPs), displaying fusion glycoproteins of Chikungunya virus (CHIKV) and a Receptor Binding Domain (RBD) of SARS-CoV-2 on its surface. The uniqueness and versatility of ChAC-VLPs have been demonstrated via various techniques, including Western blot, Immunofluorescence, cryo-EM, and Dynamic Light Scattering (DLS). The multimeric epitope display of immunogenic antigens was validated by cell-based assays. ChAC-VLP immunized mice sera have shown substantial neutralization titers for CHIKV (PRNT50 of 1:25). Similarly, serum antibodies were detected for SARS-CoV-2 RBD as observed by antigen-specific ELISA and validated using Surface Plasmon Resonance (SPR). ChAC-VLP-immunized mice sera at a 1:10 dilution exhibited 80-95 % SARS-CoV-2 pseudovirus neutralization relative to the untreated virus control. In conclusion, this study proposes ChAC-VLPs as a potential hybrid vaccine candidate for CHIKV and SARS-CoV-2 infections and contributes valuable insights into the chi-VLPs domain and its design.</p>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"805 ","pages":"153346"},"PeriodicalIF":2.2,"publicationDate":"2026-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146123528","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-23DOI: 10.1016/j.bbrc.2026.153336
Helmut Spielvogel, Eveline Schreiber, Teresa Siegert, Christoph Alexiou
<p><p>Nanoparticles can be divided into several different classes. Within these classes, iron oxide-based nanoparticles exhibiting superparamagnetic properties occupy a special place because, in contrast to a majority of organic nanoparticles, they are magnetically accumulable and can be visualized in magnetic resonance imaging (MRI). In the course of extensive research over several years, the Section for Experimental Oncology and Nanomedicine (SEON) at the University Hospital of Erlangen has developed and fabricated superparamagnetic iron-oxide nanoparticles (SPION) termed SEON<sup>Dex30</sup>. These particles consist of an iron oxide core of magnetite that over time partially oxidizes to maghemite, and an outer layer of cross-linked polysaccharide molecules (dextran). These SPIONs are intended to be employed in a clinical trial with the aim of providing evidence that they are superior to currently obtainable iron oxide nanoparticle medicinal products approved as MRI contrast media for liver imaging in terms of application safety, long-term tolerance and imaging quality. In order for a clinical trial center to be able to resort to SEON<sup>Dex30</sup> as an Investigational Medicinal Product (IMP) for human use, the particles must be manufactured according to Good Manufacturing Practice (GMP) guidelines. GMP-compliant development and production of nanomedicines requires in-depth knowledge of regulatory requirements and product-specific process technology as well as the availability of trained specialist staff, built-to-order manufacturing equipment and officially approved production areas. In the event that academic and clinical institutions lack the required financial, organisational and human resources to establish their own pharmaceutical production environment, it would seem reasonable to resort to specialised pharmaceutical companies that are able and willing to offer adequate procurement, manufacturing, quality control, certification and distribution services. Beyond the use of superparamagnetic nanoparticles as MRI contrast medium, further areas of application are being explored by SEON. In addition to dextran, other biocompatible and toxicologically safe materials such as proteins, lipids and polymers may also be used as coating agents. Functionalisation is achieved by attachment of active pharmaceutical ingredients (APIs) to the coated particle surface via chemical bonding techniques, resulting in the formation of API-loaded nanoparticles for magnetically-based accumulation, controlled drug release, targeted cancer therapies and several other application fields. The requirements on quality of starting materials, technology, production processes and quality inspections for finished SEON<sup>Dex30</sup> IMPs as described in this report may be seen as representative for other iron oxide-based nanoparticle medicinal products for human use to be developed and manufactured in the future. This article is intended as a process-oriented technical
{"title":"GMP-compliant batch manufacturing of dextran-coated iron oxide nanoparticles: A process development case study.","authors":"Helmut Spielvogel, Eveline Schreiber, Teresa Siegert, Christoph Alexiou","doi":"10.1016/j.bbrc.2026.153336","DOIUrl":"https://doi.org/10.1016/j.bbrc.2026.153336","url":null,"abstract":"<p><p>Nanoparticles can be divided into several different classes. Within these classes, iron oxide-based nanoparticles exhibiting superparamagnetic properties occupy a special place because, in contrast to a majority of organic nanoparticles, they are magnetically accumulable and can be visualized in magnetic resonance imaging (MRI). In the course of extensive research over several years, the Section for Experimental Oncology and Nanomedicine (SEON) at the University Hospital of Erlangen has developed and fabricated superparamagnetic iron-oxide nanoparticles (SPION) termed SEON<sup>Dex30</sup>. These particles consist of an iron oxide core of magnetite that over time partially oxidizes to maghemite, and an outer layer of cross-linked polysaccharide molecules (dextran). These SPIONs are intended to be employed in a clinical trial with the aim of providing evidence that they are superior to currently obtainable iron oxide nanoparticle medicinal products approved as MRI contrast media for liver imaging in terms of application safety, long-term tolerance and imaging quality. In order for a clinical trial center to be able to resort to SEON<sup>Dex30</sup> as an Investigational Medicinal Product (IMP) for human use, the particles must be manufactured according to Good Manufacturing Practice (GMP) guidelines. GMP-compliant development and production of nanomedicines requires in-depth knowledge of regulatory requirements and product-specific process technology as well as the availability of trained specialist staff, built-to-order manufacturing equipment and officially approved production areas. In the event that academic and clinical institutions lack the required financial, organisational and human resources to establish their own pharmaceutical production environment, it would seem reasonable to resort to specialised pharmaceutical companies that are able and willing to offer adequate procurement, manufacturing, quality control, certification and distribution services. Beyond the use of superparamagnetic nanoparticles as MRI contrast medium, further areas of application are being explored by SEON. In addition to dextran, other biocompatible and toxicologically safe materials such as proteins, lipids and polymers may also be used as coating agents. Functionalisation is achieved by attachment of active pharmaceutical ingredients (APIs) to the coated particle surface via chemical bonding techniques, resulting in the formation of API-loaded nanoparticles for magnetically-based accumulation, controlled drug release, targeted cancer therapies and several other application fields. The requirements on quality of starting materials, technology, production processes and quality inspections for finished SEON<sup>Dex30</sup> IMPs as described in this report may be seen as representative for other iron oxide-based nanoparticle medicinal products for human use to be developed and manufactured in the future. This article is intended as a process-oriented technical","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"805 ","pages":"153336"},"PeriodicalIF":2.2,"publicationDate":"2026-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146131170","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-23DOI: 10.1016/j.bbrc.2026.153306
Sinan Gönüllü , Şeyma Aydın , Hamit Çelik , Oğuz Çelik , Sefa Küçükler , Ahmet Topal , Ramazan Akay , M. Onur Yıldız , Bülent Alım , M.Hüdai Çulha , Selçuk Özdemir
In this study, we investigated the therapeutic potential of miR-206-3p delivered via small extracellular vesicles (sEVs) in an in vitro Alzheimer's disease model using SH-SY5Y human neuroblastoma cells treated with amyloid beta (Aβ). The sEV–miR-206-3p complexes were successfully loaded with miR-206-3p (∼0.001 copies per particle) without disrupting vesicle integrity or inducing cytotoxicity at the optimized concentration of 5 μg/mL. Aβ treatment significantly increased oxidative stress markers (ROS, MDA, LDH) and decreased antioxidant enzyme activity (SOD), while GPX1 showed an opposite trend. Furthermore, Aβ elevated proinflammatory gene expression (ICAM1, TNF-α) and reduced neuroprotective BDNF levels, induced mitochondrial dysfunction (increased Cyt-c, PINK1, DNM1L; decreased TFAM), impaired synaptic proteins (CPLX2, ROR1), and promoted tau phosphorylation and Aβ accumulation. Treatment with sEV–miR-206-3p effectively mitigated these alterations, reducing oxidative stress, suppressing neuroinflammatory responses, restoring mitochondrial function and synaptic protein levels, and attenuating tau and Aβ pathology. These findings demonstrate that miR-206-3p-loaded sEVs protect neuroblastoma cells from Aβ-induced neurodegenerative processes, highlighting their potential as a novel drug delivery system for neuroprotection.
{"title":"In vitro investigation of miR-206-3p-loaded extracellular vesicles as modulators of Aβ-induced neurodegeneration","authors":"Sinan Gönüllü , Şeyma Aydın , Hamit Çelik , Oğuz Çelik , Sefa Küçükler , Ahmet Topal , Ramazan Akay , M. Onur Yıldız , Bülent Alım , M.Hüdai Çulha , Selçuk Özdemir","doi":"10.1016/j.bbrc.2026.153306","DOIUrl":"10.1016/j.bbrc.2026.153306","url":null,"abstract":"<div><div>In this study, we investigated the therapeutic potential of miR-206-3p delivered via small extracellular vesicles (sEVs) in an in vitro Alzheimer's disease model using SH-SY5Y human neuroblastoma cells treated with amyloid beta (Aβ). The sEV–miR-206-3p complexes were successfully loaded with miR-206-3p (∼0.001 copies per particle) without disrupting vesicle integrity or inducing cytotoxicity at the optimized concentration of 5 μg/mL. Aβ treatment significantly increased oxidative stress markers (ROS, MDA, LDH) and decreased antioxidant enzyme activity (SOD), while GPX1 showed an opposite trend. Furthermore, Aβ elevated proinflammatory gene expression (ICAM1, TNF-α) and reduced neuroprotective BDNF levels, induced mitochondrial dysfunction (increased Cyt-c, PINK1, DNM1L; decreased TFAM), impaired synaptic proteins (CPLX2, ROR1), and promoted tau phosphorylation and Aβ accumulation. Treatment with sEV–miR-206-3p effectively mitigated these alterations, reducing oxidative stress, suppressing neuroinflammatory responses, restoring mitochondrial function and synaptic protein levels, and attenuating tau and Aβ pathology. These findings demonstrate that miR-206-3p-loaded sEVs protect neuroblastoma cells from Aβ-induced neurodegenerative processes, highlighting their potential as a novel drug delivery system for neuroprotection.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"802 ","pages":"Article 153306"},"PeriodicalIF":2.2,"publicationDate":"2026-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146059180","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号