The FEBS journal最新文献_第5页

The dual and context-dependent role of mast cells in cutaneous wound healing and scar formation. 肥大细胞在皮肤伤口愈合和疤痕形成中的双重和环境依赖作用。

IF 4.2

The FEBS journal Pub Date : 2026-10-08 DOI: 10.1111/febs.70757

Pooja Kushwaha, Sangita Mukhopadhyay

{"title":"The dual and context-dependent role of mast cells in cutaneous wound healing and scar formation.","authors":"Pooja Kushwaha, Sangita Mukhopadhyay","doi":"10.1111/febs.70757","DOIUrl":"https://doi.org/10.1111/febs.70757","url":null,"abstract":"Successful tissue repair depends on the precise orchestration of phase-specific cellular responses alongside sustained activity of multifunctional immune regulators. Mast cells, which have primarily been long regarded as effector cells of allergic reactions, have emerged as pivotal modulators of wound repair. Importantly, mast cell activity exhibits a dual nature: while transient activation supports efficient repair and granulation tissue formation, sustained or excessive activation is associated with pathological fibrosis, hypertrophic scarring and keloid formation. Although many experimental studies and clinical evidences implicate a critical role for mast cells in wound repair, several key questions remain. Specifically, the contributions of distinct mast cell subtypes and the precise temporal dynamics of their mediator release, as well as the intricate molecular crosstalk between mast cells, stromal components, and other infiltrating immune cells remans a subject of active investigation. This review highlights current literature on the multifaceted roles of mast cells across the successive phases of wound-healing, and the specific mechanisms by which mast cells support or impair tissue repair, outlining unresolved questions in the field. Through this discussion, we aim to provide a framework for developing new therapeutic strategies to improve healing outcomes and facilitate better scar management.","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149139763","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Multicancer analysis reveals mtDNA copy number as a key determinant of mutational load and cancer progression. 多癌分析显示mtDNA拷贝数是突变负荷和癌症进展的关键决定因素。

IF 4.2

The FEBS journal Pub Date : 2026-10-07 DOI: 10.1111/febs.70736

Anamika Acharyya, Riddhiman Dhar

{"title":"Multicancer analysis reveals mtDNA copy number as a key determinant of mutational load and cancer progression.","authors":"Anamika Acharyya, Riddhiman Dhar","doi":"10.1111/febs.70736","DOIUrl":"https://doi.org/10.1111/febs.70736","url":null,"abstract":"Mitochondrial DNA (mtDNA) copy number determines the functional state of mitochondria and thus, influences cellular energy production, growth, metabolism, and stress response. Variation in mtDNA copy number has been observed across many cancer types and has been linked to changes in gene expression. However, whether mtDNA copy number has any link to mutation accumulation in cancer is unknown. Further, how mtDNA copy number variation alters expression of cancer-associated pathways and thereby influences cancer progression remains unclear. Here, through an analysis of whole genome data in multiple cancer types, we show that mtDNA copy number increases with an increase in mutational load in cancer samples and the increase in mtDNA copy number bears a signature of compensation for mitochondrial function. We also show that the samples with low-mtDNA generally have increased expression of cancer-promoting genes, including genes involved in cell migration and epithelial-mesenchymal transition (EMT). Taken together, these results reveal a close association of mtDNA copy number with mutational load and disease progression in cancer. These findings provide a way forward toward a better understanding of the role of mtDNA copy number and mitochondrial functional state in cancer progression.","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149121377","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Correction to "Engineered T7 RNA polymerase reduces dsRNA formation by lowering terminal transferase and RNA-dependent RNA polymerase activities". 修正“工程T7 RNA聚合酶通过降低末端转移酶和RNA依赖的RNA聚合酶活性来减少dsRNA的形成”。

IF 4.2

The FEBS journal Pub Date : 2026-10-07 DOI: 10.1111/febs.70735

引用次数: 0

Combining TAG-72CAR with anti-MUC16CAR improves the potency of ovarian cancer treatment. TAG-72CAR联合抗muc16car可提高卵巢癌的治疗效果。

IF 4.2

The FEBS journal Pub Date : 2026-10-06 DOI: 10.1111/febs.70760

Alicia Villatoro, Aurore Dougé, Klara Krpina, Lea-Marie Schmitz, Christopher Forcados, Fatemeh Kaveh, Andrea Estrella Arias-Díaz, Pascal Gelebart, Emmet McCormack, Renata Stripecke, Miguel Abal, Ben Davidson, Else Marit Inderberg, Sébastien Wälchli

{"title":"Combining TAG-72CAR with anti-MUC16CAR improves the potency of ovarian cancer treatment.","authors":"Alicia Villatoro, Aurore Dougé, Klara Krpina, Lea-Marie Schmitz, Christopher Forcados, Fatemeh Kaveh, Andrea Estrella Arias-Díaz, Pascal Gelebart, Emmet McCormack, Renata Stripecke, Miguel Abal, Ben Davidson, Else Marit Inderberg, Sébastien Wälchli","doi":"10.1111/febs.70760","DOIUrl":"https://doi.org/10.1111/febs.70760","url":null,"abstract":"Ovarian cancer (OC) is typically associated with poor prognosis and high mortality. Chimeric antigen receptor (CAR) T-cell therapy offers a promising strategy, yet its application in solid tumours remains constrained by limited efficacy and on-target/off-tumour toxicities. We previously developed K101CAR T cells targeting CA125, the cleaved extracellular domain of MUC16, and demonstrated potent antitumour activity against OC. However, because MUC16 exhibits low-level expression in certain normal tissues, safety concerns remain regarding potential off-tumour effects. We designed a combinatorial CAR composed of two single-chain variable fragments (scFvs): (i) TAG-72 targeting the Sialyl-Tn antigen highly expressed on malignant cells, and (ii) the K101 scFv. The first unit is linked to a CD3ζ signalling domain, whereas the second is linked to a 4-1BB costimulatory domain, leading to a combinatorial CAR fully reactive against double-positive targets, Tz-KBBCAR. We demonstrate that Tz-KBBCAR T cells efficiently eliminate MUC16+/TAG-72+-, while sparing MUC16+/TAG-72-- cells in vitro and markedly suppress tumour progression in vivo. We also observed that compared to K101CAR T cells, Tz-KBBCAR T cells exhibit enhanced expansion, sustained viability, and a reduced exhaustion phenotype. Overall, our study presents an efficient combinatorial CAR T-cell strategy predicted to be safer than single CAR T-cell therapy for OC.","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149121334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Emerging therapeutic strategies to target APOE4 in Alzheimer's disease. 针对APOE4治疗阿尔茨海默病的新治疗策略。

IF 4.2

The FEBS journal Pub Date : 2026-10-05 DOI: 10.1111/febs.70759

Wei I Jiang, Bingying Wang, Dengke K Ma

{"title":"Emerging therapeutic strategies to target APOE4 in Alzheimer's disease.","authors":"Wei I Jiang, Bingying Wang, Dengke K Ma","doi":"10.1111/febs.70759","DOIUrl":"https://doi.org/10.1111/febs.70759","url":null,"abstract":"The apolipoprotein E ε4 (APOE4) allele is the strongest common genetic risk factor for late-onset Alzheimer's disease. However, its incomplete penetrance supports the view that it acts as a modifiable systems-level perturbation of brain homeostasis rather than a deterministic driver. Increasing evidence further positions APOE4 protein within interconnected lipid metabolic pathways, with converging genetic, epidemiological, and translational studies implicating disrupted cholesterol transport, lipoprotein metabolism, and lipid oxidation as upstream mechanisms that promote neurodegeneration. Here, we synthesize currently developing therapeutic strategies targeting APOE4 across domains: small molecules, endogenous protectors, emerging biologics, and systemic lipid modulators. Small molecules include structural correctors and natural compounds, while endogenous protection arises from APOE2, the APOE3-Christchurch variant, and modifiers such as CASP7, KLOTHO, the VHL-HIF axis, fibronectin, and NHE6-mediated endosomal regulation. Biologic platforms enable allele-selective and pathway-specific interventions via siRNA, antisense oligonucleotides, and antibodies targeting pathological APOE conformers. In parallel, cholesteryl ester transfer protein (CETP) inhibition has emerged as a systems-level strategy that restores lipid and redox homeostasis, with early clinical evidence showing reductions in neurodegenerative biomarkers, particularly in APOE4 carriers. These advances support an integrative therapeutic framework to restore brain lipid homeostasis, stress resilience and neural-vascular coupling, positioning APOE4 as a modifiable node within a preventable lipid-vascular-neurodegenerative axis.","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149121352","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Dimerization of human PARP15 is required for NAD⁺ binding and automodification. 人类PARP15的二聚化是NAD+结合和自修饰所必需的。

IF 4.2

The FEBS journal Pub Date : 2026-10-05 DOI: 10.1111/febs.70758

Anna Tuovinen, Johan Pääkkönen, Mirko M Maksimainen, Lea Hirschen, Heli I Hentilä, Marie Tauscher, Bernhard Lüscher, Carlos Vela-Rodríguez, Patricia Korn, Lari Lehtiö

{"title":"Dimerization of human PARP15 is required for NAD+ binding and automodification.","authors":"Anna Tuovinen, Johan Pääkkönen, Mirko M Maksimainen, Lea Hirschen, Heli I Hentilä, Marie Tauscher, Bernhard Lüscher, Carlos Vela-Rodríguez, Patricia Korn, Lari Lehtiö","doi":"10.1111/febs.70758","DOIUrl":"https://doi.org/10.1111/febs.70758","url":null,"abstract":"PARP proteins are enzymes catalyzing ADP-ribosylation, a well-conserved post-translational modification. In addition to the catalytic domain present in all PARPs, these proteins have a wide variety of other domains possessing different functions. Additional domains present in human PARP15 are macrodomains, capable of binding ADP-ribose. PARP15 is the least studied of the macrodomain-containing human PARPs, and it is linked to different diseases from infections to cancer. We show that the full-length canonical isoform 1 of PARP15 auto-ADP-ribosylates robustly on glutamate and aspartate residues, from which the modification can be hydrolyzed by known ADP-ribosylhydrolases. We have been able to locate several modification sites in the region of tandem macrodomains. Consistent with previous findings that the catalytic domain dimerization is necessary for enzymatic activity, we confirm this in the full-length context with the recombinant isoform 1 of PARP15. We show that dimerization is required for the efficient substrate NAD+ binding, and we provide structural basis for this requirement with the help of a co-crystal structure of the catalytic domain dimer with an unhydrolyzable substrate analog.","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149121350","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Identification of genes encoding GRF transcription factors in Taraxacum kok-saghyz Rodin and their potential role in response to salt stress. 蒲公英GRF转录因子编码基因的鉴定及其在盐胁迫响应中的潜在作用

IF 4.2

The FEBS journal Pub Date : 2026-10-05 DOI: 10.1111/febs.70756

Yifeng Cheng, Zhuanzhuan Jiang, Rongrong Sun, Wenhui Rao, Yuxian Yang, Shubao Hu, Youyang Qin, Wenyue Han, Yuanping Zhu, Ziyan Yu, Junbo Wang, Anqi Su, Binbin Zhao, Jing Wang, Jiashun Miao, Xiaojian Peng

{"title":"Identification of genes encoding GRF transcription factors in Taraxacum kok-saghyz Rodin and their potential role in response to salt stress.","authors":"Yifeng Cheng, Zhuanzhuan Jiang, Rongrong Sun, Wenhui Rao, Yuxian Yang, Shubao Hu, Youyang Qin, Wenyue Han, Yuanping Zhu, Ziyan Yu, Junbo Wang, Anqi Su, Binbin Zhao, Jing Wang, Jiashun Miao, Xiaojian Peng","doi":"10.1111/febs.70756","DOIUrl":"https://doi.org/10.1111/febs.70756","url":null,"abstract":"GRF transcription factors (GRF) are pivotal regulators of plant development and stress tolerance, but their functional repertoire in the rubber crop Taraxacum kok-saghyz (Russian dandelion) remains entirely uncharacterized. Genome-wide analysis of the T. kok-saghyz genome identified 10 TkGRF members, unevenly distributed across eight chromosomes and phylogenetically resolved into five clades. All TkGRFs contained the canonical QLQ and WRC domains, confirming their identity as bona fide GRF transcription factors. Synteny analysis further established close evolutionary conservation of these 10 TkGRF members with Asteraceae relatives, while promoter profiling revealed pervasive cis-regulatory elements linked to hormonal and stress signaling, pointing to a broad regulatory potential. Integrated RNA-seq and qRT-PCR analyses confirmed the tissue-specific expression profiles of TkGRFs under salt stress. Notably, TkGRF1, a nucleus-localized transcription factor displaying transcriptional activation activity, exhibited the most robust response to stress. Overexpression of TkGRF1 in Arabidopsis resulted in elevated Malondialdehyde (MDA) and reactive oxygen accumulation, while lowering antioxidant enzyme activities, confirming its negative role in salt tolerance. RNA-seq further uncovered salt-triggered transcriptional reprogramming of hormone signaling, energy metabolism and stomatal development pathways. This study lays a theoretical basis and offers a potential target for the molecular breeding of salt-tolerant T. kok-saghyz.","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149121336","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

PICH facilitates iPSC reprogramming by alleviating genomic instability induced by DNA replication stress PICH通过减轻DNA复制胁迫引起的基因组不稳定性，促进iPSC重编程。

IF 4.2

The FEBS journal Pub Date : 2026-10-01 Epub Date: 2026-04-14 DOI: 10.1111/febs.70550

Fengjiao Zhang, Chaoran Ji, Fang Ji, Chao Zhang, Hongwei Liao, Zhehua Shao, Fang Jia, Xinwei Geng, Songmin Ying

{"title":"PICH facilitates iPSC reprogramming by alleviating genomic instability induced by DNA replication stress","authors":"Fengjiao Zhang, Chaoran Ji, Fang Ji, Chao Zhang, Hongwei Liao, Zhehua Shao, Fang Jia, Xinwei Geng, Songmin Ying","doi":"10.1111/febs.70550","DOIUrl":"10.1111/febs.70550","url":null,"abstract":"Somatic cell reprogramming to induced pluripotent stem cells (iPSCs) holds great promise for revolutionizing tissue repair and regenerative medicine. However, achieving high reprogramming efficiency remains challenging due to various endogenous or exogenous barriers. One major obstacle is DNA replication stress arising from rapid cell proliferation during iPSC reprogramming, which results in genomic instability and markedly reduced reprogramming efficiency. The Plk1-interacting checkpoint helicase [PICH; also known as DNA excision repair protein ERCC-6-like (ERCC6L)], a member of the SNF2 ATPase family, is pivotal in maintaining genomic stability by promoting sister chromatid disjunction upon replication stress. Our previous work revealed that PICH is essential for maintaining the genomic stability of embryonic hematopoietic stem cells, but whether and how PICH participates in iPSC reprogramming remains elusive. We show that PICH deficiency induces genomic instability and drastically reduces the efficiency of iPSC generation. Overexpression of Pich improves iPSC reprogramming efficiency by alleviating replication stress. Furthermore, PICH cooperates with telomere-associated protein RIF1, another protein required for sister chromatid disjunction, to maintain genomic stability in iPSCs, thereby enhancing reprogramming efficiency. Taken together, these results reveal a previously unknown role of PICH in facilitating the reprogramming of iPSCs via maintaining genomic stability under replication stress, and provide a new strategy for improving iPSC reprogramming efficiency.","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":"293 19","pages":"5908-5921"},"PeriodicalIF":4.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147694367","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Ultrafast python-integrated single-entity electrochemical sensor for detecting glycated albumin 用于糖化白蛋白检测的超快蟒蛇集成单实体电化学传感器。

IF 4.2

The FEBS journal Pub Date : 2026-10-01 Epub Date: 2026-04-18 DOI: 10.1111/febs.70547

Zihni Onur Uygun

引用次数: 0

KU80 suppresses endonuclease G activity to preserve genomic integrity KU80抑制内切酶G活性以保持基因组完整性。

IF 4.2

The FEBS journal Pub Date : 2026-10-01 Epub Date: 2026-03-16 DOI: 10.1111/febs.70495

Jargalan Batsaikhan, Kwang-Hyun Park, Hae Ryung Chang, Eunyoung Jung, Myung-Jin Kim, Jeeyoon Kang, Hyunjo Shim, Eui-Jeon Woo, Yonghwan Kim

{"title":"KU80 suppresses endonuclease G activity to preserve genomic integrity","authors":"Jargalan Batsaikhan, Kwang-Hyun Park, Hae Ryung Chang, Eunyoung Jung, Myung-Jin Kim, Jeeyoon Kang, Hyunjo Shim, Eui-Jeon Woo, Yonghwan Kim","doi":"10.1111/febs.70495","DOIUrl":"10.1111/febs.70495","url":null,"abstract":"Endonuclease G (ENDOG) is involved in DNA replication, mitochondrial DNA maintenance, and late apoptosis. Its role in genome maintenance and cell death necessitates strict regulation to prevent unwanted DNA damage. Although inhibitors of ENDOG have been identified in nonmammalian species, no such inhibitors have been discovered in mammals. Here, we identify KU80 as a novel negative regulator of ENDOG in human cells. The KU80 C-terminal domain (CTD) shares structural homology with Drosophila EndoG inhibitor (EGI), directly binds ENDOG and inhibits its nuclease activity in vitro. In silico modeling and immunoprecipitation reveal the KU80 core domain mediates ENDOG interaction. Depletion of KU80 increases nuclear ENDOG accumulation and DNA damage under normal conditions, evidenced by elevated phosphorylated histone H2AX (γH2AX) levels. Conversely, ENDOG-deficient cells show reduced DNA damage and increased chemotherapeutic resistance. We uncover a mechanism where KU80 maintains genomic stability by inhibiting ENDOG activity and nuclear translocation. This study establishes KU80 as a key DNA damage response regulator, offering insights into potential therapies for diseases linked to dysregulated ENDOG activity.","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":"293 19","pages":"5952-5966"},"PeriodicalIF":4.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/febs.70495","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147470636","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0