The FEBS journal最新文献_第4页

Chromogenic and FRET peptide substrates, quantum-dot peptide conjugates and electrochemical peptide interfaces: A 25-year journey from combinatorial chemistry to clinical readouts-A viewpoint. 显色和FRET肽底物，量子点肽偶联物和电化学肽界面：从组合化学到临床读数的25年之旅-一个观点。

IF 4.2

The FEBS journal Pub Date : 2026-10-13 DOI: 10.1111/febs.70729

Adam Lesner, Natalia Gruba, Magdalena Wysocka

{"title":"Chromogenic and FRET peptide substrates, quantum-dot peptide conjugates and electrochemical peptide interfaces: A 25-year journey from combinatorial chemistry to clinical readouts-A viewpoint.","authors":"Adam Lesner, Natalia Gruba, Magdalena Wysocka","doi":"10.1111/febs.70729","DOIUrl":"https://doi.org/10.1111/febs.70729","url":null,"abstract":"This Viewpoint synthesises 25 years of work from a single laboratory on activity-based protease sensing and offers a critical appraisal of where each of the three resulting platforms stands today. The activity of proteolytic enzymes-rather than their abundance-determines the outcome of inflammation, tumour progression, viral entry and barrier dysfunction. Measuring it in clinical samples is demanding: closely related proteases share substrate preferences, and biological matrices are crowded with endogenous inhibitors and competing hydrolases. Over the past 25 years, our group at the University of Gdansk has developed a chemical toolkit along three complementary axes, assembled here, as a probe ladder running from solution chemistry to solid-state interface. First, internally quenched chromogenic and Förster resonance energy transfer (FRET) peptide substrates, designed by iterative deconvolution of combinatorial libraries spanning non-primed and primed subsites, provide selective readouts for serine, cysteine, metallo- and viral proteases. Second, peptide-quantum dot conjugates built on non-toxic ZnO nanocrystals improved detection limits 20-30-fold over the parent solution substrate in two published demonstrators. Third, peptide-modified gold electrodes translate protease cleavage and molecular recognition into a label-free electrochemical signal-exemplified by an electrode that reads 20S proteasome activity and by an antimicrobial-peptide interface for bacterial endotoxin. We applied the resulting probes in exploratory studies of bladder cancer, type-2 diabetes and diabetic nephropathy, and positioned them within the broader landscape of activity-based protease sensing-the activity-based probes of the Bogyo and Cravatt laboratories, the PS-SCL and HyCoSuL combinatorial approaches, and the Weissleder near-infrared imaging program.","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149187254","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

A comparative analysis of cell death signalling in RNA and DNA virus infections and potential inhibitory strategies. RNA和DNA病毒感染中细胞死亡信号传导和潜在抑制策略的比较分析。

IF 4.2

The FEBS journal Pub Date : 2026-10-13 DOI: 10.1111/febs.70763

Panagiotis Keramidas, Maria Pitou, Amalia Aggeli, Sotiris Varlamis, Theodora Choli-Papadopoulou

{"title":"A comparative analysis of cell death signalling in RNA and DNA virus infections and potential inhibitory strategies.","authors":"Panagiotis Keramidas, Maria Pitou, Amalia Aggeli, Sotiris Varlamis, Theodora Choli-Papadopoulou","doi":"10.1111/febs.70763","DOIUrl":"https://doi.org/10.1111/febs.70763","url":null,"abstract":"The recent COVID-19 pandemic and the epidemic outbreak of Mpox have demonstrated that viruses, despite their apparently simple structure, are sophisticated microorganisms that have evolved complicated pro-survival mechanisms. Their potential to manipulate cell death pathways can affect and determine the outcome of the infection cycle and the host's immune response. RNA viruses typically display a more acute and aggressive nature, as they often promote cell death. In this way, they proliferate and release their virions to infect adjacent cells and perpetuate their life cycle. Common consequences of RNA virus infection include hyperinflammatory responses in hosts, typically leading in damage to the epithelial barrier. Conversely, DNA viruses modulate these pathways to sustain a balance between the lytic cycle, during which they replicate, and latency, wherein they remain inactive until an appropriate stimulus triggers reactivation. Achieving this balance and transitioning between stages of infection requires the inhibition of cellular death processes. In both instances, the viruses seem to respond to the cellular context, enhancing their adaptability through mutations, so to deceive host defenses and therefore secure their survival. This highlights the necessity to comprehend the processes via which these biological threats induce cell death, thereby facilitating the development of broad-spectrum or targeted antiviral treatments.","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149187277","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

A guide to studying tumour-T-cell interactions using in vitro coculture assays. 使用体外共培养法研究肿瘤- t细胞相互作用的指南。

IF 4.2

The FEBS journal Pub Date : 2026-10-13 DOI: 10.1111/febs.70765

Nooshin Khoshdoozmasouleh, Conor J Kearney

{"title":"A guide to studying tumour-T-cell interactions using in vitro coculture assays.","authors":"Nooshin Khoshdoozmasouleh, Conor J Kearney","doi":"10.1111/febs.70765","DOIUrl":"https://doi.org/10.1111/febs.70765","url":null,"abstract":"T cells are central mediators of antitumour immunity and are the cellular basis of many successful cancer immunotherapies, including immune checkpoint blockade, T-cell receptor (TCR)-engineered therapies and chimeric antigen receptor (CAR) T cells. However, clinical responses remain variable, and many tumours evade or resist T-cell-mediated control. Understanding how T cells recognise tumour cells, deliver cytotoxic signals, produce inflammatory cytokines and shape tumour cell fate is therefore essential for improving modern immunotherapies. In vitro tumour T-cell coculture systems provide a powerful experimental framework for dissecting these processes under controlled conditions. They allow investigators to manipulate antigen specificity, HLA/MHC restriction, tumour genotype, T-cell activation state, cytokine exposure and drug-mediated perturbation in ways that are difficult to achieve in vivo. However, these systems require careful design, because assay outcomes are strongly influenced by tumour model, antigen expression, effector-to-target ratio, assay duration and readout. This guide provides a practical framework for studying tumour T-cell interactions in vitro, with a focus on CD8+ T-cell-mediated tumour recognition and killing. It discusses commonly used mouse and human antigen-specific models, how antigen expression and presentation can be experimentally controlled, T-cell activation and coculture conditions, cytotoxicity assays, immune synapse imaging, competition assays, cytokine-mediated bystander killing, transcriptional profiling, CRISPR perturbation strategies, therapeutic testing and patient-derived models. The aim is to help researchers choose the most appropriate model, experimental setup and readout for the biological question being asked and to avoid common interpretive pitfalls when studying tumour immune sensitivity, resistance and therapeutic response.","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149187275","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

Caloric restriction alters early renal responses to reversible obstructive nephropathy in rats. 热量限制改变了可逆性阻塞性肾病大鼠的早期肾脏反应。

IF 4.2

The FEBS journal Pub Date : 2026-10-13 DOI: 10.1111/febs.70744

Polina A Abramicheva, Ilya A Sokolov, Dmitry S Semenovich, Vasily N Manskikh, Nadezda V Andrianova, Ljubava D Zorova, Irina B Pevzner, Milana A Berezhnaia, Egor Y Plotnikov

{"title":"Caloric restriction alters early renal responses to reversible obstructive nephropathy in rats.","authors":"Polina A Abramicheva, Ilya A Sokolov, Dmitry S Semenovich, Vasily N Manskikh, Nadezda V Andrianova, Ljubava D Zorova, Irina B Pevzner, Milana A Berezhnaia, Egor Y Plotnikov","doi":"10.1111/febs.70744","DOIUrl":"https://doi.org/10.1111/febs.70744","url":null,"abstract":"Obstructive nephropathy is a renal pathology caused by impaired urinary outflow. Although ureteral occlusion in clinical practice is often reversible, the recovery phase after obstruction relief remains incompletely understood and lacks mechanism-based interventions. Caloric restriction (CR) is widely considered a nephroprotective strategy and has shown therapeutic potential in several models of kidney injury. In this study, we investigated whether a 35% CR pretreatment for 4 weeks modulates the early postobstructive renal response in a rat model of reversible unilateral ureteral obstruction (R-UUO). Pretreatment with CR did not enhance early kidney recovery 24 h after restoration of urine flow, as evaluated by serum creatinine, urea, and renal injury markers. During this phase, CR also failed to improve fibrosis and tissue remodeling markers (α-SMA, MMP2, Tgfb1). However, CR was associated with reduced renal Ngal expression and a shift in the inflammatory response, characterized by lower neutrophil infiltration. Meanwhile, macrophage markers CD163, Cd206, and Tlr2 remained elevated. CR altered acetylation-related molecular response, including opposite shifts in acetylation of histone H3 and histone H4, increased SIRT3, and decreased SIRT1, and resulted in selective preservation of oxidative phosphorylation complex I. These data indicate that under severe postobstructive kidney injury, CR induces selective inflammatory and metabolic-epigenetic remodeling without clear early morphofunctional rescue. Mitochondrial function and epigenetic plasticity appear to be CR-responsive elements, while timing and severity of injury appear critical for manifestation of phenotypic nephroprotection. Thus, development of more targeted CR protocols or CR mimetics may be required to translate observed molecular shifts into morphofunctional benefit.","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149187296","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 'Species barrier as molecular basis for adaptation of synthetic prions with N-terminally truncated PrP'. 修正“物种屏障是合成朊病毒适应n端截断PrP的分子基础”。

IF 4.2

The FEBS journal Pub Date : 2026-10-09 DOI: 10.1111/febs.70755

引用次数: 0

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