FEBS Open Bio最新文献

Pharmacological inhibition of the PERK pathway modulates hepatocellular carcinoma growth and immune signaling 药理抑制PERK通路调节肝细胞癌的生长和免疫信号。

IF 2.7 4区生物学

FEBS Open Bio Pub Date : 2026-09-04 Epub Date: 2026-04-21 DOI: 10.1002/2211-5463.70252

Ada Lerma-Clavero, Maria Kopsida, Nathalie Arendt, Hans Lennernäs, Markus Sjöblom, Femke Heindryckx

{"title":"Pharmacological inhibition of the PERK pathway modulates hepatocellular carcinoma growth and immune signaling","authors":"Ada Lerma-Clavero, Maria Kopsida, Nathalie Arendt, Hans Lennernäs, Markus Sjöblom, Femke Heindryckx","doi":"10.1002/2211-5463.70252","DOIUrl":"10.1002/2211-5463.70252","url":null,"abstract":"The unfolded protein response (UPR) plays an important role in tumor progression and cellular stress adaptation. In hepatocellular carcinoma (HCC), pharmacological inhibition of the protein kinase R-like endoplasmic reticulum kinase (PERK) is a potential therapeutic strategy, yet its effects on tumor growth and the microenvironment remain unclear. We investigated the selective PERK inhibitor AMG PERK 44 in a diethylnitrosamine (DEN)-induced mouse model of advanced HCC. Tumor burden, proliferation, fibrosis, immune-related gene expression, and ER stress signaling were assessed alongside analyses of single-cell RNA-sequencing data from HCC mouse models and liver-specific PERK knockout mice. Our results show that AMG PERK 44 did not alter tumor number nor cause a decrease in tumor area and proliferation. Furthermore, fibrotic burden was unchanged, although fibrosis architecture and stromal gene expression (TGF-β, CTGF, F4/80) were modified. Despite PERK inhibition, the expression of ER stress associated genes (CHOP, EIF2AK3, ERdj4) increased. Single-cell analysis revealed context-dependent PERK activity, highest in dendritic cells and macrophages under inflammatory and tumor conditions, while PERK knockout livers showed impaired UPR responses after tunicamycin treatment. Finally, AMG PERK 44 did not enhance idarubicin efficacy and caused no major off-target effects. These findings highlight the context-dependent role of PERK in the HCC microenvironment and its implications for targeting UPR pathways in liver cancer.\u0000 ","PeriodicalId":12187,"journal":{"name":"FEBS Open Bio","volume":"16 9","pages":"1766-1785"},"PeriodicalIF":2.7,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13398901/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147766847","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Evaluating GenAI-produced feedback on undergraduate bioscience essays against good higher education feedback practice. 评估genai对本科生物科学论文的反馈与良好的高等教育反馈实践。

IF 2.7 4区生物学

FEBS Open Bio Pub Date : 2026-09-04 DOI: 10.1002/2211-5463.70339

Annabel Court, Nigel Francis, Andrew Shore, Stephen Rutherford

{"title":"Evaluating GenAI-produced feedback on undergraduate bioscience essays against good higher education feedback practice.","authors":"Annabel Court, Nigel Francis, Andrew Shore, Stephen Rutherford","doi":"10.1002/2211-5463.70339","DOIUrl":"https://doi.org/10.1002/2211-5463.70339","url":null,"abstract":"The emergence of generative artificial intelligence (GenAI) has led to substantial interest in its potential to support student learning and assessment in higher education. In particular, GenAI's ability to provide immediate and iterative formative feedback on the quality of students' work has substantial potential to enhance student learning and attainment. However, for feedback to be impactful and useful, the quality and utility of feedback generated by GenAI needs to accurately reflect the quality of the work and align with principles for good feedback provision. This study evaluated the feedback that an undergraduate student might obtain from a single, unscaffolded interaction with a GenAI platform (ChatGPT4o), without tutor input, applied to 30 Year 1 Bioscience essays. Using a bespoke rubric for feedback quality alongside qualitative and quantitative analyses, the GenAI-generated feedback was evaluated for alignment to established hallmarks of good feedback practice. Overall, GenAI-authored feedback had useful elements but was limited in scope. While feedback tended to be accurate, specific to the essay, with a strong focus on content and substantial elements of feed-forward advice, critical guidance and motivational feedback were limited. Within the feedback test, neutral observations focused mostly on structure and use of figures. Positive feedback focused mainly on use of language, and areas for improvement mostly on structure, missing content, and citations/references. These findings suggest that GenAI may have some potential to provide instant, formative guidance to students, but its use may require substantial scaffolding by educators in order to be effective.","PeriodicalId":12187,"journal":{"name":"FEBS Open Bio","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148891448","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Long-term hippocampal alterations and cognitive impairment in a murine model of surgical sepsis 外科败血症小鼠模型的长期海马改变和认知障碍。

IF 2.7 4区生物学

FEBS Open Bio Pub Date : 2026-09-04 Epub Date: 2026-04-16 DOI: 10.1002/2211-5463.70240

Dong Seong Cho, Rebecca Schmitt, Aneesha Dasgupta, Alexandra Ducharme, Jason Doles

{"title":"Long-term hippocampal alterations and cognitive impairment in a murine model of surgical sepsis","authors":"Dong Seong Cho, Rebecca Schmitt, Aneesha Dasgupta, Alexandra Ducharme, Jason Doles","doi":"10.1002/2211-5463.70240","DOIUrl":"10.1002/2211-5463.70240","url":null,"abstract":"Cognitive impairment in sepsis survivors is a growing clinical challenge as the number of sepsis cases rise and acute mortality rates fall. It is estimated that up to 70% of sepsis patients experience cognitive dysfunction and many report persistent dysfunction post-sepsis. Cognitive impairment is a broad term that refers to sepsis-associated brain dysfunction or encephalopathy (SABD or SAE, respectively). While many contributors, such as inflammation, blood–brain barrier dysfunction, and extended microglial activation are implicated in SABD/SAE development, much is still unknown regarding the underlying mechanistic causes of persistent cognitive defects in sepsis survivors. Here, we employed cecal ligation and puncture (CLP) to model surgical sepsis in mice, after which mice were subjected to multiple memory function assays for up to 2 months post-sepsis. Furthermore, single-cell RNA sequencing and validation studies were performed with murine hippocampi to query alterations in the brain microenvironment. Our study shows that CLP mice exhibited decreased spontaneous alternation at 4 weeks and decreases in both short- and long-term recognition (at 6 weeks and 2 weeks, respectively) accompanied by substantially altered cell type makeup of the hippocampus, including hippocampal neuron and pericyte loss. Finally, transcriptional alterations in the macrophage populations implicate aberrant activation in CLP survivors. In conclusion, post-sepsis mice exhibit reduced memory capacity and altered hippocampal cell composition and transcriptional profiles. This study and associated data set will be valuable for further investigation of the underlying pathophysiology of SABD/SAE and elucidation of potential therapeutic candidates.","PeriodicalId":12187,"journal":{"name":"FEBS Open Bio","volume":"16 9","pages":"1657-1668"},"PeriodicalIF":2.7,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13398903/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147697303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Acute caffeine treatment protects the developing retina from ischemia-induced cell death 急性咖啡因治疗可保护发育中的视网膜免受缺血引起的细胞死亡。

IF 2.7 4区生物学

FEBS Open Bio Pub Date : 2026-09-04 Epub Date: 2026-05-13 DOI: 10.1002/2211-5463.70251

Amanda Alves Nascimento, Danniel Pereira-Figueiredo, Gabriella Grossi de Lima Dias, Gabriel Ferreira dos Santos, Mariana Rodrigues Pereira, Rafael Brito, Karin C Calaza

{"title":"Acute caffeine treatment protects the developing retina from ischemia-induced cell death","authors":"Amanda Alves Nascimento, Danniel Pereira-Figueiredo, Gabriella Grossi de Lima Dias, Gabriel Ferreira dos Santos, Mariana Rodrigues Pereira, Rafael Brito, Karin C Calaza","doi":"10.1002/2211-5463.70251","DOIUrl":"10.1002/2211-5463.70251","url":null,"abstract":"Ischemic damage to the retina during development can lead to irreversible neuronal loss, driven in part by excitotoxic mechanisms and energy deprivation. While two-day caffeine exposure has previously been shown to confer neuroprotection in this context, it remained unclear whether acute administration during an ischemic event could yield similar benefits. In this study, we used an ex vivo model of oxygen and glucose deprivation (OGD) in chick embryo retinas to investigate whether a single, acute dose of caffeine applied during the insult reduces cell death and engages intracellular survival pathways. Results showed a significant reduction in OGD-induced cytotoxicity by caffeine exposure. However, unlike in the context of chronic exposure, acute caffeine exposure did not increase BDNF expression. Furthermore, antioxidant agents failed to mimic caffeine's protective effects, and acute caffeine exposure did not induce the expression of antioxidant response genes, nor oxidative stress or VEGF expression, suggesting that oxidative stress mitigation is not the primary mechanism for this effect. However, pharmacological antagonism of adenosine A2A receptors with ZM241385 reproduced the neuroprotective effects of caffeine and reduced extracellular glutamate levels during OGD. These findings indicate that acute caffeine administration protects the developing retina primarily through A2A receptor antagonism and inhibition of glutamate excitotoxicity, rather than by activating canonical survival signaling pathways. This supports the potential use of caffeine as a rapid neuroprotective agent during acute ischemic events in the immature central nervous system.","PeriodicalId":12187,"journal":{"name":"FEBS Open Bio","volume":"16 9","pages":"1726-1740"},"PeriodicalIF":2.7,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13399045/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147928004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

How phagocytic cells kill bacteria: Lessons from a professional killer 吞噬细胞如何杀死细菌：来自职业杀手的经验教训。

IF 2.7 4区生物学

FEBS Open Bio Pub Date : 2026-09-04 Epub Date: 2026-06-27 DOI: 10.1002/2211-5463.70280

Otmane Lamrabet, Pierre Cosson

{"title":"How phagocytic cells kill bacteria: Lessons from a professional killer","authors":"Otmane Lamrabet, Pierre Cosson","doi":"10.1002/2211-5463.70280","DOIUrl":"10.1002/2211-5463.70280","url":null,"abstract":"Professional phagocytic cells such as neutrophils and macrophages, as well as free-living soil amoebae like Dictyostelium discoideum, employ evolutionarily conserved mechanisms to ingest and kill bacteria. Ingested bacteria are killed in phagosomes by four main antibacterial systems: production of reactive oxygen and nitrogen species, accumulation of bactericidal ions, deployment of lysosomal enzymes, and release of membrane-permeabilizing peptides. Despite extensive studies, important questions persist. How complete is the list of known antibacterial mechanisms? What is their relative contribution to bacterial destruction? How specific are they for different bacterial species? This review examines how D. discoideum amoebae and mammalian phagocytes ingest and eliminate non-pathogenic bacteria, focusing on three specific elements: the dual role of lysozyme, the specificity of antibacterial mechanisms, and the redundancy of the antibacterial arsenal. Overall, our current knowledge highlights the sophisticated strategies employed by phagocytes against diverse microorganisms. It also provides a framework to study the more complex interactions between phagocytic cells and pathogenic bacteria.","PeriodicalId":12187,"journal":{"name":"FEBS Open Bio","volume":"16 9","pages":"1637-1644"},"PeriodicalIF":2.7,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13399256/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148338345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

MARK4 enhances stress granule formation under oxidative stress and increases tau accumulation. MARK4促进氧化应激下应激颗粒的形成，增加tau蛋白的积累。

IF 2.7 4区生物学

FEBS Open Bio Pub Date : 2026-09-04 DOI: 10.1002/2211-5463.70338

Sho Nakajima, Kotone Watanabe, Grigorii Sultanakhmetov, Aoi Fukuchi, Keiya Ito, Sawako Shimizu, Taro Saito, Akiko Asada, Kanae Ando

引用次数: 0

Identifying gene expression signatures for risk stratification of postoperative adjuvant chemotherapy in colorectal cancer 确定结直肠癌术后辅助化疗风险分层的基因表达特征。

IF 2.7 4区生物学

FEBS Open Bio Pub Date : 2026-09-04 Epub Date: 2026-03-30 DOI: 10.1002/2211-5463.70243

Mayuko Otomo, Keisuke Okuno, Shuichi Watanabe, Sakiko Oba, Hiroyasu Kagawa, Masanori Tokunaga, Daisuke Ban, Yusuke Kinugasa

{"title":"Identifying gene expression signatures for risk stratification of postoperative adjuvant chemotherapy in colorectal cancer","authors":"Mayuko Otomo, Keisuke Okuno, Shuichi Watanabe, Sakiko Oba, Hiroyasu Kagawa, Masanori Tokunaga, Daisuke Ban, Yusuke Kinugasa","doi":"10.1002/2211-5463.70243","DOIUrl":"10.1002/2211-5463.70243","url":null,"abstract":"Clinical risk stratification for postoperative recurrence in patients with pathological stage II (pStage II) colorectal cancer (CRC) is essential for guiding the use of postoperative adjuvant chemotherapy (ACT). In this study, we identified novel prognostic gene expression biomarkers in patients with pStage II CRC and developed a new risk stratification framework for ACT decision-making. First, genome-wide biomarker discovery was conducted to identify prognostic gene expression biomarkers associated with recurrence risk in pStage II CRC. This analysis identified 10 differentially expressed genes as potential biomarkers for recurrence. The efficacy of these biomarkers was then tested using 188 clinical surgical specimens obtained from patients with pStage II CRC. A predictive panel was developed using qRT-PCR and used to assess 93 clinical specimens with an area under the curve (AUC) of 0.82, and its performance was further validated in an independent cohort (n = 95). By incorporating key clinicopathological features, a Gene expression-based Prediction of Recurrence in pStage II CRC (GPRSC) signature was developed, which robustly predicted postoperative recurrence (AUC: 0.80). Finally, combining the GPRSC signature, microsatellite instability status, and conventional criteria, we developed a novel risk stratification system for postoperative ACT decision-making in pStage II CRC. Overall, we identified novel gene expression biomarkers and developed a prognostic signature that informs clinical decision-making regarding postoperative ACT in patients with pStage II CRC.","PeriodicalId":12187,"journal":{"name":"FEBS Open Bio","volume":"16 9","pages":"1813-1824"},"PeriodicalIF":2.7,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13398948/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147581090","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

YIPFα1A expression is regulated by multilayered molecular mechanisms yipf - α 1a的表达受多层分子机制调控。

IF 2.7 4区生物学

FEBS Open Bio Pub Date : 2026-09-04 Epub Date: 2026-04-06 DOI: 10.1002/2211-5463.70244

Tokio Takaji, Yurika Nakanishi, Nobuhiro Nakamura

{"title":"YIPFα1A expression is regulated by multilayered molecular mechanisms","authors":"Tokio Takaji, Yurika Nakanishi, Nobuhiro Nakamura","doi":"10.1002/2211-5463.70244","DOIUrl":"10.1002/2211-5463.70244","url":null,"abstract":"Yip domain family (YIPF) proteins are five-pass transmembrane proteins that localize primarily to the Golgi apparatus. These proteins assemble into higher-order complexes with each α-subunit pairing specifically with a β-subunit to form a dimer which then assemble into complexes with two to four dimers. Notably, β-subunit expression depends on the corresponding α-subunit partner, and conventional transient overexpression of α-subunits has been extremely inefficient, hindering deeper analysis of YIPF complexes. To identify the cause of poor exogenous expression, we examined YIPF gene features and found two properties correlated with low expression: (i) rare-codon enrichment in the CDS and (ii) extended 3′ UTRs. Experimental analyses focusing on YIPFα1A revealed that rare-codon enrichment suppresses expression mainly at the mRNA level, consistent with translation-coupled mRNA decay, whereas inclusion of the native 3′ UTR enhances expression by increasing mRNA abundance. Deletion mapping further showed that a proximal 3′ UTR segment (51–150) is necessary and sufficient for mRNA stabilization, thereby elevating both mRNA and protein levels. Conversely, a distal 3′ UTR fragment (1116–2230) increased mRNA but not protein levels, suggesting translational repression resulting in a reduced protein-to-mRNA ratio. Together, these findings explain the discrepancy between endogenous and exogenous YIPFα1A expression and propose a multilayered regulatory model in which rare codons decrease mRNA, the proximal 3′ UTR stabilizes mRNA, and the distal 3′ UTR reduces translation.\u0000 ","PeriodicalId":12187,"journal":{"name":"FEBS Open Bio","volume":"16 9","pages":"1669-1690"},"PeriodicalIF":2.7,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13398756/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147622151","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Derivation and characterization of retinal pigment epithelium from urine-derived iPSCs 尿源性多能干细胞视网膜色素上皮的衍生和表征。

IF 2.7 4区生物学

FEBS Open Bio Pub Date : 2026-09-04 Epub Date: 2026-04-24 DOI: 10.1002/2211-5463.70246

Daniella Beiner, Hainan Zhu, Carol Christine Bosholm, Heuy-Ching Wang, Tracy Criswell, Anthony Atala, Jian-Xing Ma, Yuanyuan Zhang

{"title":"Derivation and characterization of retinal pigment epithelium from urine-derived iPSCs","authors":"Daniella Beiner, Hainan Zhu, Carol Christine Bosholm, Heuy-Ching Wang, Tracy Criswell, Anthony Atala, Jian-Xing Ma, Yuanyuan Zhang","doi":"10.1002/2211-5463.70246","DOIUrl":"10.1002/2211-5463.70246","url":null,"abstract":"Age-related macular degeneration (AMD), particularly its dry form, is a leading cause of irreversible vision loss due to retinal pigment epithelium (RPE) dysfunction and loss. Addressing this unmet therapeutic need requires non-invasive strategies for generating patient-specific RPE cells. This study reports the successful generation and initial characterization of RPE cells derived from urine-derived induced pluripotent stem cells (u-iPSC-RPE). Urine-derived stem cells (USCs) were isolated from healthy individuals and comprehensively characterized, confirming strong expression of renal progenitor makers and mesenchymal stem cell markers, while lacking standard hematopoietic markers. USCs were reprogrammed into iPSCs using the integration-free Sendai virus expressing the Yamanaka factors. The reprogrammed u-iPSC clones displayed characteristic pluripotency marker expression and demonstrated clearance of the Sendai virus by later passages. Subsequently, these u-iPSCs were efficiently differentiated into RPE cells, exhibiting characteristic hexagonal morphology and pigmentation which was confirmed by the expression of key RPE-specific proteins. Our findings demonstrate the feasibility and reliability of generating patient-specific u-iPSC-RPE cells from readily accessible USCs providing a foundation for future studies to investigate their functional potential for retinal disease modeling and therapeutic applications for AMD.","PeriodicalId":12187,"journal":{"name":"FEBS Open Bio","volume":"16 9","pages":"1691-1707"},"PeriodicalIF":2.7,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13398809/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147766770","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Establishing an assay to evaluate d-amino acid oxidase enzyme kinetics and inhibition using WST-8 redox dye 建立了WST-8氧化还原染料对d-氨基酸氧化酶酶动力学及抑制作用的评价方法。

IF 2.7 4区生物学

FEBS Open Bio Pub Date : 2026-09-04 Epub Date: 2026-02-24 DOI: 10.1002/2211-5463.70217

Kahoko Miyake, Yuki Enoki, Yuka Nakazawa, Kazuaki Taguchi, Kazuaki Matsumoto

{"title":"Establishing an assay to evaluate d-amino acid oxidase enzyme kinetics and inhibition using WST-8 redox dye","authors":"Kahoko Miyake, Yuki Enoki, Yuka Nakazawa, Kazuaki Taguchi, Kazuaki Matsumoto","doi":"10.1002/2211-5463.70217","DOIUrl":"10.1002/2211-5463.70217","url":null,"abstract":"d-Amino acid oxidase (DAO) inhibitors are novel candidate therapeutic agents for neurodegenerative diseases. In this study, a novel inhibition assay using WST-8 as a detection reagent was developed and its effectiveness for evaluating redox-based enzyme kinetics was tested. Furthermore, using this assay, we also investigated the inhibitory activities of uremic toxins and endogenous amino acid metabolites. Briefly, a mixture of DAO, WST-8, and d-amino acids was allowed to react in phosphate buffer and DAO activity was detected as an increase in absorbance when both d-serine and DAO were present. However, as reducing compounds could potentially cause false-positive results, we confirmed that the detection of DAO activity in this system was mediated by the redox reaction of WST-8. Critically, we verified that this assay could be used to evaluate the inhibitory activity of known DAO inhibitors, including uremic toxins which showed weak DAO inhibition. This study establishes an alternative assay system that can be utilized for assessing DAO-inhibitory activity and other enzymatic reactions mediated by redox reactions.","PeriodicalId":12187,"journal":{"name":"FEBS Open Bio","volume":"16 9","pages":"1645-1656"},"PeriodicalIF":2.7,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13398905/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147276080","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0