生物学最新文献

{"title":"Human TBC1 domain-containing kinase is a class I multidomain pseudokinase.","authors":"Shiwangi Maurya, Lilly E Cheek, Anthony T Iavarone, Wen Zhu","doi":"10.1016/j.pep.2026.106989","DOIUrl":"10.1016/j.pep.2026.106989","url":null,"abstract":"<p><p>TBCK-related encephalopathy (TBCKE) is a neurodevelopmental disorder associated with biallelic mutations in TBCK. Despite the increasing number of reported cases worldwide, the biochemical and biophysical properties of TBCK remain unclear, hindering molecular understanding of its role in disease. Here, we report the successful expression and purification of full-length human TBCK using Spodoptera frugiperda cells. Biochemical and biophysical analyses reveal that the catalytically inactive pseudokinase domain of TBCK lacks nucleotide binding, consistent with the absence of the canonical VAIK, HRD, and DFG motifs required for catalysis. These findings support that TBCK is a class I pseudokinase and provide a foundation for future structural and functional studies to elucidate its biological role.</p>","PeriodicalId":20757,"journal":{"name":"Protein expression and purification","volume":" ","pages":"106989"},"PeriodicalIF":1.8,"publicationDate":"2027-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13502288/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148670679","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}

{"title":"Exploring the putative role of EGFR in prostate cancer: Interactions with androgen and estrogen receptors.","authors":"G M Gonçalves, D S Souza, C R M Costa, M E G Oliveira, C S Porto, C M Vicente","doi":"10.1016/j.jsbmb.2026.107101","DOIUrl":"10.1016/j.jsbmb.2026.107101","url":null,"abstract":"<p><p>The epidermal growth factor receptor (EGFR) is a transmembrane tyrosine kinase receptor that plays a critical role in regulating cell proliferation, survival, and differentiation. Aberrant activation or overexpression of EGFR has been observed in several cancers, including prostate cancer (PCa), and is associated with aggressive tumor behavior and poor prognosis. The development and progression of PCa largely depend on the involvement of androgen receptor (AR) pathways, which are directly related to EGFR signaling. Research indicates that EGFR can affect AR activity, increasing transcriptional activity or promoting ligand-independent activation, which may lead to castration-resistant prostate cancer (CRPC). Furthermore, emerging evidence suggests that estrogen receptors (ERs) may also interact with EGFR signaling in prostate tissue. These may influence tumor growth, interactions with cellular plasticity, and therapy resistance, but their exact mechanisms require further investigation. Identifying and improving treatment strategies for advanced and treatment-resistant PCa requires understanding the interplay between the EGFR, AR, and ER pathways. However, clinical trials have shown limited success in targeting EGFR alone, possibly through compensatory mechanisms via steroid hormone receptors. Therefore, therapies that simultaneously target EGFR and AR/ER activity may be more effective. Continued research into the molecular interplay between these pathways will broaden our understanding of prostate cancer biology and support the development of more personalized and effective treatments. In this review will focus on EGFR/HER1 and its putative role in prostate cancer. Furthermore, we discuss the potential interaction between EGFR, androgen receptor (AR), and estrogen receptor (ER) signaling pathways.</p>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":" ","pages":"107101"},"PeriodicalIF":3.1,"publicationDate":"2027-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148708523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tissue-predominant estrogen metabolic remodeling in adenomyosis revealed by LC-MS/MS profiling.","authors":"Qing Wang, BoYang Liu, Lei Kuang, Lingke Wang, Yingying Chou, Bei Zhang, Guiping Wan, Tao Gui","doi":"10.1016/j.jsbmb.2026.107095","DOIUrl":"10.1016/j.jsbmb.2026.107095","url":null,"abstract":"<p><p>Adenomyosis (AM) is an estrogen-dependent gynecological disorder in which local steroid handling may contribute to clinical heterogeneity. To characterize estrogen metabolic features in AM, we used liquid chromatography-tandem mass spectrometry (LC-MS/MS) to quantify 13 estrogens and estrogen metabolites in endometrial tissue and serum. Tissue metabolite profiles showed marked increases in catechol estrogens, particularly 2-hydroxyestrone (2-OHE1) and 4-hydroxyestrone (4-OHE1), whereas serum changes were more limited, with 2-methoxyestrone (2-MeOE1) representing the main circulating difference. Pathway- and ratio-based analyses indicated enhanced hydroxylation in tissue without a proportionate increase in downstream methylation-related readouts. Correlation and regression analyses further showed that tissue 2-OHE1 and 4-OHE1 were independently associated with dysmenorrhea severity. In exploratory receiver operating characteristic analyses performed within the discovery cohort, tissue catechol estrogens showed stronger discriminatory ability than serum metabolites. These findings suggested that AM was associated with endometrial tissue-predominant remodeling of estrogen metabolism rather than with generalized elevation of parent estrogens. The present study identified candidate metabolic markers requiring further validation and provided a framework for future investigation of local steroid metabolism in AM.</p>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":" ","pages":"107095"},"PeriodicalIF":3.1,"publicationDate":"2027-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148631999","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Repurposing nitazoxanide as a novel ferroptosis inducer for triple-negative breast cancer via dual disruption of iron homeostasis and the β-catenin/GPX4 axis.","authors":"Chenshan Zhang, Ting Yang, Yuxuan Meng, Yao Zou, Ying Lu, Wenjun Wang, Sakorn Pornprasert, Wuga Jiwa, Tao He, Yan Lin","doi":"10.1080/13510002.2026.2695689","DOIUrl":"https://doi.org/10.1080/13510002.2026.2695689","url":null,"abstract":"<p><strong>Background: </strong>Ferroptosis induction is a promising triple-negative breast cancer (TNBC) therapy, but current inducers are suboptimal. Nitazoxanide (NTZ), an FDA-approved antiparasitic with anticancer and redox activity, may be repurposed as a ferroptosis inducer, yet its effects and mechanisms in TNBC are unclear.</p><p><strong>Methods: </strong>Anti-TNBC effects of NTZ were assessed in MDA-MB-231 and Hs578T cells via viability, clonogenicity, migration/invasion, and zebrafish xenografts. Ferroptosis was evaluated by iron levels, lipid peroxidation, GSH/GSSG, MDA, ROS, and mitochondrial TEM. Mechanisms were studied by docking, western blot, qPCR, apoptosis assay, cycloheximide chase, and pharmacological rescue.</p><p><strong>Results: </strong>NTZ inhibited proliferation, migration, and invasion in vitro and tumor growth in vivo, and induced ferroptosis. Mechanistically, it disrupted iron homeostasis by upregulating TFR1 and downregulating FPN1, causing iron overload and lipid peroxidation, and promoted β-catenin degradation, which transcriptionally suppressed GPX4, weakening antioxidant defense. Both β-catenin stabilization and ferroptosis inhibition reversed these effects.</p><p><strong>Conclusion: </strong>NTZ is repurposed as a ferroptosis inducer for TNBC via dual disruption of iron homeostasis and β-catenin/GPX4 axis, providing a strong preclinical rationale for its therapeutic use.</p>","PeriodicalId":21096,"journal":{"name":"Redox Report","volume":"31 1","pages":"2695689"},"PeriodicalIF":6.9,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148346206","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of starvation-driven diffusions and diverse interspecific competitions on species coexistence and fitness.","authors":"Youngseok Chang, Inkyung Ahn, Wonhyung Choi","doi":"10.1080/17513758.2026.2623563","DOIUrl":"10.1080/17513758.2026.2623563","url":null,"abstract":"<p><p>This study examines competition models based on the Lotka-Volterra form that incorporate starvation-driven diffusions (SDD). Such dispersal assumes that species disperse in response to resource abundance or scarcity in a heterogeneous habitat. The primary objective of this study is to examine how SDD, in combination with diverse interspecific interactions, affects species' fitness and coexistence states. To this end, the study introduces a refined classification for competing interactions based on a novel metric that quantifies the variability of resource heterogeneity across the environment. This approach contrasts with traditional models that assume uniform diffusion within homogeneous environments. This study investigates the local stability of two semitrivial steady states and establishes the existence and uniqueness of positive steady states by eigenvalue analysis and monotone dynamical systems theory. Through this analytical exploration, the study reveals that the interplay between species' dispersal strategies and the varying intensities of interspecific competition significantly impacts ecological outcomes.</p>","PeriodicalId":48809,"journal":{"name":"Journal of Biological Dynamics","volume":"20 1","pages":"2623563"},"PeriodicalIF":2.7,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146107532","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stability and bifurcation analysis of a discrete plankton system with holling Type-II predation and toxin effects.","authors":"Abdou Al Zubaidi, Muhammad Rafaqat, Jihad Younis, Syed Tauseef Saeed","doi":"10.1080/17513758.2026.2619269","DOIUrl":"10.1080/17513758.2026.2619269","url":null,"abstract":"<p><p>This work examines the dynamics of a discrete-time plankton interaction model, in which phytoplankton generate toxins and are vulnerable to external contamination. The model includes a Holling Type-II predation response and uses a piecewise constant argument approach to break it up into smaller pieces. This keeps the ecological realism of the continuous system while making it possible to study complex discrete-time behaviors. Our focus is on the formation of Neimark-Sacker bifurcation, a phenomena associated with the initiation of quasi-periodic oscillations in population densities. We show how toxin buildup and outside contamination can make plankton populations unstable, which could cause blooms to happen in an irregular way, using stability analysis and numerical simulations. The results show how useful discrete-time models are for capturing rapid changes in ecosystems, such damaging algal blooms. They also give ideas for managing ecosystems and reducing blooms.</p>","PeriodicalId":48809,"journal":{"name":"Journal of Biological Dynamics","volume":"20 1","pages":"2619269"},"PeriodicalIF":2.7,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146126880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction.","authors":"","doi":"10.1080/13510002.2026.2645268","DOIUrl":"10.1080/13510002.2026.2645268","url":null,"abstract":"","PeriodicalId":21096,"journal":{"name":"Redox Report","volume":"31 1","pages":"2645268"},"PeriodicalIF":7.4,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12983813/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147444876","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction.","authors":"","doi":"10.1080/13510002.2026.2648349","DOIUrl":"10.1080/13510002.2026.2648349","url":null,"abstract":"","PeriodicalId":21096,"journal":{"name":"Redox Report","volume":"31 1","pages":"2648349"},"PeriodicalIF":7.4,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13015051/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147504926","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluating ancestry adjustment in multi-ancestry epigenome-wide analysis.","authors":"Yueming Liu, Alan Kuang, Marie-France Hivert, William L Lowe, Jami L Josefson, Denise M Scholtens","doi":"10.1080/15592294.2026.2646063","DOIUrl":"10.1080/15592294.2026.2646063","url":null,"abstract":"<p><p>Proper adjustment for population substructure is essential in epigenome-wide association studies (EWAS), particularly in cohorts with diverse ancestries. EPISTRUCTURE offers a genotype-free approach to ancestry inference, originally developed using a European reference population from the Cooperative Health Research in the Region of Augsburg (KORA) study. However, its effectiveness in genetically diverse, multi-ancestry cohorts remains insufficiently evaluated. For EWAS using cord-blood samples from the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study, we systematically assessed the ancestry adjustment performance of EPISTRUCTURE principal components (PCs) derived from the widely used KORA-based reference set versus new reference sets generated from genotyping data of the multi-ancestry HAPO cohort. HAPO-based reference sets were defined by varying SNP - CpG <math><mrow><msup><mi>R</mi><mn>2</mn></msup></mrow></math> thresholds (e.g. RS30: <math><mrow><msup><mi>R</mi><mn>2</mn></msup></mrow><mo>></mo><mn>0.3</mn></math>) to identify ancestry-informative CpGs. We applied these reference sets for population substructure adjustment in EWAS of three newborn adiposity traits, birthweight, cord C-peptide, and sum of skinfolds, to evaluate their impact on association detection and biological interpretation. Compared to the KORA reference, the HAPO RS30 reference consistently produced lower genomic inflation and identified more biologically relevant associations for birthweight and cord blood C-peptide in EWAS of HAPO cord blood samples (<i>n</i> = 3,116). Pathway enrichment analyses revealed strong immune and metabolic signals, including pathways uniquely captured by EWAS when using the HAPO-derived reference for ancestry adjustment. Trait enrichment using the EWAS Catalog further confirmed associations with fetal growth, maternal metabolic traits, and glucose regulation. Our findings demonstrate that reference sets derived from multi-ancestry cohorts like HAPO better capture underlying population substructure and improve ancestry adjustment in diverse EWAS settings.</p>","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"21 1","pages":"2646063"},"PeriodicalIF":3.7,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147485090","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}

{"title":"M6A-dependent regulation of microRNAs from CKD stage 5 patients: insights from epigenetic modification analysis.","authors":"Zhiqian Yang, Fanna Liu, Mingjun Ye, Qiang Yan, Zhipeng Zeng, Jingsheng Ma, Haitao Li, Hualin Ma, Xinzhou Zhang, Xiaofeng Zhu, Yong Dai, Donge Tang","doi":"10.1080/15592294.2026.2653962","DOIUrl":"10.1080/15592294.2026.2653962","url":null,"abstract":"<p><p>Chronic kidney disease (CKD) stage 5 is frequently accompanied by systemic inflammation, and peripheral blood mononuclear cells (PBMCs) play an important role. To define the epitranscriptomic features of PBMC small RNAs in CKD stage 5, we profiled N6-methyladenosine (m6A) using small RNA modification microarrays. A total of 158 miRNAs, 149 pre-miRNAs, and 197 tsRNAs showed differential m6A modification. Enrichment analysis implicated PI3K-Akt, p53 signalling, and leukocyte transendothelial migration. Integrating target prediction with GEO transcriptomic datasets identified IRF1 and RUNX2 as key targets. MeRIP confirmed reduced m6A in miR-205-3p and miR-93-5p, accompanied by upregulation of RUNX2 and downregulation of IRF1 by qPCR. These results define an altered m6A-modification profile of PBMC small RNAs in CKD stage 5 and highlight miRNA-target gene axes with potential biomarker utility.</p>","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"21 1","pages":"2653962"},"PeriodicalIF":3.7,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147632646","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}