Bioscience Reports最新文献

{"title":"Redox status of apolipoprotein E in cerebrospinal fluid: a mechanistically informative biomarker for central nervous system disorders.","authors":"Yui Uematsu, Wakana Iinuma, Riho Shimizu, Hiroto Matsuura, Tsuneaki Yoshinaga, Masahide Yazaki, Kazuyoshi Yamauchi","doi":"10.1042/BSR20250388","DOIUrl":"10.1042/BSR20250388","url":null,"abstract":"<p><p>Apolipoprotein (apo) E is the major cholesterol carrier in the central nervous system (CNS); however, the clinical relevance of its cysteine-thiol redox status in cerebrospinal fluid (CSF) remains unclear. We investigated whether CSF apoE redox indices (redox-IDX-apoE) reflect cholesterol transport efficiency and disease-specific pathologies. We quantified reduced (red), reversibly oxidized (roxi), and irreversibly oxidized (oxi) apoE in CSF and serum using a maleimide-based band-shift assay. We analyzed relationships between redox-IDX-apoE, CSF cholesterol (TC) level, and the TC/apoE ratio (inverse transport efficiency) in patients with apoE3/E3 and identified transport determinants using isometric log-ratio (ILR) regression. Significant but only moderate correlations between CSF and serum indices suggested distinct redox behavior in the two compartments. ApoE3/E4 carriers exhibited higher oxi-apoE, reflecting reduced buffering capacity. In apoE3/E3 CSF, aging increased roxi/total and decreased red/roxi, suggesting a shift toward oxidized forms. CSF TC levels positively correlated with roxi-related indices. Conversely, the TC/apoE ratio negatively correlated with red/roxi, indicating that red-apoE supports higher efficiency. ILR analysis confirmed that maintaining the reduced monomeric state, rather than the reversibly oxidized form, was independently associated with improved transport efficiency. Diagnostic groups exhibited distinct signatures: neurodegenerative disorders showed elevated irreversible oxidation, whereas neuroimmunological and infectious conditions exhibited profiles suggestive of reversible and acute oxidation, respectively. The CSF apoE redox status links local redox balance to cholesterol handling and reflects CNS pathophysiology. Maintaining reduced cysteine-thiol appears important for functional capacity, whereas a shift toward oxidation reflects a trade-off between buffering ability and transport efficiency. These indices may serve as potential biomarkers.</p>","PeriodicalId":8926,"journal":{"name":"Bioscience Reports","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13181357/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147761290","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retraction: Silencing microRNA-27a inhibits proliferation and invasion of human osteosarcoma cells through the SFRP1-dependent Wnt/β-catenin signaling pathway.","authors":"Yuanyuan Shi, Junfeng Li, Yu Mu, Lina Zhang, Xue Chen, Si Chen","doi":"10.1042/BSR20182366_RET","DOIUrl":"10.1042/BSR20182366_RET","url":null,"abstract":"","PeriodicalId":8926,"journal":{"name":"Bioscience Reports","volume":"46 5","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13189526/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147962025","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combined effects of lncRNA MIR17HG polymorphisms and lifestyle-related risk factors on the development and progression of tongue squamous cell carcinoma.","authors":"Yi-Chieh Yang, Yi-Fang Ding, Chiao-Wen Lin, Yu-Fan Liu, Kuo-Hao Ho, Lun-Ching Chang, Shun-Fa Yang, Ming-Hsien Chien","doi":"10.1042/BSR20260002","DOIUrl":"10.1042/BSR20260002","url":null,"abstract":"<p><p>Oral squamous cell carcinoma is the most common malignancy of the oral cavity, with tongue squamous cell carcinoma (TSCC) being particularly prevalent worldwide. Evidence suggests that the long noncoding RNA, miRNA 17-92a-1 cluster host gene (MIR17HG), plays dual roles in tumor development. However, its clinical relevance and genetic variation in TSCC remain unclear. Analysis of data from TCGA revealed that MIR17HG expression is significantly up-regulated in head and neck squamous cell carcinoma, particularly in male and Asian populations. The present study examined the association between MIR17HG single-nucleotide polymorphisms (SNPs) and TSCC progression in Taiwanese men. Four tagging SNPs (rs1428, rs7318578, rs17735387, and rs75267932) were genotyped through a TaqMan allelic discrimination assay. The results revealed that rs75267932 G allele carriers had a significantly elevated risk of developing large tumors in the dominant genetic model. This association was more prominent in patients exposed to one of the environmental carcinogens, including betel quid, cigarette smoke, or alcohol. Smokers or drinkers carrying the rs75267932 variant were also likely to present with advanced disease. When patients with TSCC were stratified by exposure to all three lifestyle-related risk factors, the effect of rs75267932 on disease progression became the strongest. Conversely, non-betel-quid chewers or nonsmokers carrying the variant had a reduced risk of high-grade tumors. Overall, the effect of rs75267932 on TSCC progression was most pronounced in individuals exposed to lifestyle-related risk factors. These findings unveil gene-environment interactions in TSCC and highlight MIR17HG polymorphisms as potential biomarkers for risk assessment and disease monitoring in Asian men.</p>","PeriodicalId":8926,"journal":{"name":"Bioscience Reports","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13181356/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147509447","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of low-dose lithium supplementation on thermal inactivation of SERCA in cardiac muscle of male mice.","authors":"Sophie I Hamstra, Mia S Geromella, Panagiota Klentrou, Peter M Tiidus, Rebecca E K MacPherson, Val A Fajardo","doi":"10.1042/BSR20253525","DOIUrl":"10.1042/BSR20253525","url":null,"abstract":"<p><p>The sarco(endo)plasmic reticulum calcium (Ca2+)-ATPase 2 (SERCA2) is a crucial regulator of cardiac muscle function that is sensitive to changes in the cellular environment, such as increased oxidative stress. This can be observed in heat stress experiments, where the thermal inactivation of SERCA is linked to an increased production of reactive oxygen species. Previous studies have shown that regulatory proteins, including phospholamban (PLN) and heat shock protein 70 (Hsp70), can physically bind to SERCA2, preserving its function in the face of heat stress. Furthermore, we have demonstrated that the inhibition of glycogen synthase kinase 3β (GSK3β) can alter the protein levels of PLN and HSP70 in cardiac tissues obtained from male mice; however, its potential downstream effects on the thermal inactivation of SERCA have not yet been investigated. In the present study, we examined the potential effects of GSK3β inhibition through six weeks of low-dose lithium chloride supplementation (LiCl, 10 mg/kg body mass/day via drinking water) on the thermal inactivation of left ventricle SERCA2 obtained from male C57BL/6J mice. Our results show that LiCl supplementation increased inhibitory serine 9 phosphorylation on GSK3β while also significantly raising SERCA2 content and the SERCA2:PLN ratio. There were no changes to Hsp70 with LiCl supplementation. Although LiCl decreased baseline maximal SERCA activity, the decline in activity in response to heat stress was less compared with control. In conclusion, GSK3β inhibition with LiCl is associated with protection of SERCA from thermal inactivation in the heart, and future studies should explore the underlying cellular mechanisms.</p>","PeriodicalId":8926,"journal":{"name":"Bioscience Reports","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13181358/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147761258","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tissue-specific factors that govern the sialoglycan-Siglec axis in cancer.","authors":"Jamie Wills, Adam Duxfield, Manuella Siaka Monthe, Emma Scott","doi":"10.1042/BSR20250119","DOIUrl":"10.1042/BSR20250119","url":null,"abstract":"<p><p>Aberrant sialylation is a persistent glycosylation change in cancer that reshapes interactions within the tumour microenvironment through the display of sialylated glycans (sialoglycans) on malignant and stromal cells. Many sialoglycans engage sialic acid-binding immunoglobulin-like lectins (Siglecs), a family of receptors expressed predominantly by immune cells that frequently transmit inhibitory signals and function as glyco-immune checkpoints. Increasing evidence indicates that tumour hypersialylation suppresses myeloid and lymphoid anti-tumour activity, promotes immune evasion, and contributes to metastatic behaviour. However, both sialoglycan repertoires and Siglec expression patterns vary markedly across cancer types and disease states, suggesting strong dependence on tissue context and tumour composition. In the present review, we discuss how tissue-of-origin programmes and lineage state establish basal sialyltransferase expression and constrain the sialoglycan landscape available to tumours. We highlight emerging single-cell evidence that stromal populations, particularly cancer-associated fibroblasts, can acquire hypersialylation and actively generate immunosuppressive Siglec ligands. We also examine how transcriptional and oncogenic regulators, including SOX2, MYC, and androgen receptor signalling, reprogramme sialyltransferase expression to produce tumour-specific sialoglycan profiles. Finally, we consider how standard-of-care therapies alter both ligand availability and immune composition, thereby dynamically modifying the sialoglycan-Siglec axis during treatment and resistance. Understanding these context-dependent determinants will be critical for interpreting sialylation in cancer biology and for designing effective therapeutic strategies targeting sialoglycan-Siglec interactions.</p>","PeriodicalId":8926,"journal":{"name":"Bioscience Reports","volume":"46 5","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13185128/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147939852","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retraction: Dysregulation of Fra1 expression by Wnt/β-catenin signalling promotes glioma aggressiveness through epithelial-mesenchymal transition.","authors":"Huaijun Liu, Li Zhang, Xiaodan Mu, Jianling Cui, Zhigang Peng","doi":"10.1042/BSR20160643_RET","DOIUrl":"10.1042/BSR20160643_RET","url":null,"abstract":"","PeriodicalId":8926,"journal":{"name":"Bioscience Reports","volume":"46 5","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13189528/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147926000","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differential glucose uptake response to IGF-II and vesiculin in insulin-resistant muscle and adipose cells.","authors":"Thai Nguyen, Caren Leemberg, Kate L Lee","doi":"10.1042/BSR20250378","DOIUrl":"10.1042/BSR20250378","url":null,"abstract":"<p><p>Type 2 diabetes (T2D), a significant global health concern, is characterised by insulin resistance and progressive pancreatic β-cell degradation leading to failure of blood glucose regulation. Pancreatic islet hormones are essential for systemic glucose homeostasis, and their dysregulation is implicated in T2D pathogenesis. Characterisation of these hormones has been critical for understanding disease progression and designing therapeutic approaches. Vesiculin is a two-chain peptide derived from insulin-like growth factor-II (IGF-II) via a four-amino-acid excision. Studies of IGF-II and vesiculin revealed comparable insulin-like glucoregulatory activity in mice; however, in insulin-resistant animal models, vesiculin activity remains intact, whereas IGF-II activity is impeded, highlighting potential pharmacological relevance for vesiculin. We aimed to compare the glucoregulatory activity of vesiculin and IGF-II in differentiated 3T3-L1 adipocytes and L6-GLUT4myc myoblasts under insulin-sensitive and insulin-resistant conditions to understand tissue-specific activities of these peptides. Further, we characterised binding efficiency of vesiculin and IGF-II to several IGF-binding proteins (IGFBPs). Vesiculin exhibited glucose uptake comparable to IGF-II in both cell types, with similar dose response curves. Vesiculin retained efficacy in insulin-resistant myotubes, whereas IGF-II activity was blunted; however, both peptides were not significantly impacted by insulin resistance in adipocytes. Vesiculin also showed a modest synergistic effect with insulin in resistant adipocytes. Additionally, binding assays revealed that vesiculin had significantly lower affinity for IGFBP3 and IGFBP5 compared with IGF-II. These findings demonstrate that vesiculin exhibits a distinct glucoregulatory signalling profile from IGF-II, discernible specifically under insulin-resistant conditions despite their structural similarity.</p>","PeriodicalId":8926,"journal":{"name":"Bioscience Reports","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13185126/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147375927","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Patient-derived AMOTL1 mutations lead to defective cell migration and tissue development.","authors":"Jiaqian Luo, Ruxin Jin, Fang Geng, Yunying Wang, Yuwen Zhu, Wenqiang Gao, Wei Gao, Jian Li, Yaming Jiu, Ruilin Zhang, Fa-Xing Yu, Yu Wang","doi":"10.1042/BSR20250149","DOIUrl":"10.1042/BSR20250149","url":null,"abstract":"<p><p>Angiomotin-like 1 (AMOTL1), by regulating cell-cell junctions, cell polarity, and cell migration, plays a critical role in organogenesis and development. Recently, multiple studies have identified two hotspot mutations in AMOTL1, Arg157 (R157) and Pro160 (P160), in more than ten distinct families presenting with a spectrum of congenital defects, including facial dysmorphisms and cardiac abnormalities. However, the underlying pathogenic mechanism remains elusive. R157 and P160 are located in the highly conserved Tankyrase-binding motif (TBM) of AMOTL1. Here, we show that both the R157C and P160L mutants fail to interact with Tankyrase 1/2 and Ring finger protein 146, rendering them unable to undergo poly ADP-ribosylation, ubiquitination, and subsequent proteasomal degradation. As a result, these mutants are significantly stabilized and accumulate in the cytoplasm. Accumulated AMOTL1 mutants, in turn, disrupt cell junctions and focal adhesions, thereby inhibiting both the velocity and persistence of cell migration. Furthermore, during zebrafish embryonic development, expression of the R157C mutant leads to craniofacial malformations and defects in cardiac function and skeletal muscle. Our study confirms the role of AMOTL1 mutations in tissue development and uncovers the pathogenic mechanism at both molecular and cellular levels.</p>","PeriodicalId":8926,"journal":{"name":"Bioscience Reports","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13161331/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147761329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Using iPSC models to examine neuron-glia interactions in neurodegenerative diseases.","authors":"Dianne M Lopez, Lois K Keavey, Kathryn R Bowles","doi":"10.1042/BSR20250131","DOIUrl":"10.1042/BSR20250131","url":null,"abstract":"<p><p>Neurodegenerative diseases remain without effective or accessible treatments and interventions, despite their increasing global burden. Clinically, these disorders are characterised by progressive cognitive decline, behavioural changes, and loss of motor function, all of which are associated with neuronal and synaptic loss or dysfunction. Although traditionally viewed as neuron-centric, it is becoming increasingly clear that glial cells play critical roles in maintaining and regulating neuronal and synaptic health. Mounting evidence implicates glial dysregulation in both the onset and progression of neurodegenerative diseases through mechanisms such as aberrant synaptic engulfment and protein clearance, impaired homeostatic support, metabolic dysfunction, chronic inflammation, transmission of pathogenic proteins, and cellular senescence. Elucidating how disruptions in neuron-glia interactions contribute to neuronal dysfunction is therefore essential for developing effective therapies. Induced pluripotent stem cell (iPSC)-based models provide a powerful platform to investigate these interactions in human-relevant systems. Here, we will discuss recent insights into the mechanisms contributing to neurodegenerative disease that have been gained specifically from modelling neuron-glia interactions in human iPSCs.</p>","PeriodicalId":8926,"journal":{"name":"Bioscience Reports","volume":"46 5","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13161353/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147833023","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rational design framework for fluorescent biosensors from periplasmic binding proteins.","authors":"Martín González-Andrade, Abril Gijsbers, Alejandro Sosa-Peinado, Nathaly Vasquez-Martínez","doi":"10.1042/BSR20260131","DOIUrl":"10.1042/BSR20260131","url":null,"abstract":"<p><p>Periplasmic binding proteins (PBPs) are attractive scaffolds for fluorescent biosensors because they undergo large ligand-induced conformational changes and exhibit high specificity. Despite their potential, generalizable design strategies have been hindered by an incomplete understanding of how labeling positions influence protein dynamics and signal transduction. Here, we established a systematic experimental framework using the lysine-arginine-ornithine binding protein (LAO) as a model to characterize PBP-based fluorescent biosensors. Seven positions classified as endosteric, peristeric, or allosteric relative to the binding site were labeled with monobromobimane (mBBr). Our characterization revealed position-dependent effects on quantum yields, fluorescence intensity changes, ligand-binding affinities, and thermal stability. Molecular dynamics simulations (MD) of wild-type and mBBr-labeled variants provided a mechanistic context for these experimental observations. Functional biosensor positions (D51C, D53C, K228C, Y230C, and E167C) maintained open-like conformations necessary for signal generation upon ligand encounter. In contrast, peristeric position A89C, located at the hinge region, spontaneously adopted a closed-like conformation even in the absence of ligand, resulting in an inverse fluorescence response and reduced affinity. These results demonstrate that while structural criteria can guide initial site selection, experimental validation remains essential, as static structures alone cannot predict the complex interactions among labeling position, dynamics, and biosensor function. The experimental and computational framework established here with LAO as a model system provides methodological principles that may inform biosensor engineering from other PBP scaffolds, while emphasizing that conformational dynamics must be considered alongside static structural criteria.</p>","PeriodicalId":8926,"journal":{"name":"Bioscience Reports","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13161334/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147688033","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}