FEBS Open Bio最新文献

{"title":"Cyclic azapeptide CD36 ligand attenuates cardiac injury and reduces long-chain fatty acid accumulation after myocardial ischemia-reperfusion in mice.","authors":"Jade Gauvin, Naghme Radmannia, David N Huynh, Liliane Ménard, Caroline Daneault, Maïté Veilleux, Ahsanullah Ahsanullah, André C Carpentier, William D Lubell, Matthieu Ruiz, Huy Ong, Sylvie Marleau, Simon-Pierre Gravel","doi":"10.1002/2211-5463.70265","DOIUrl":"https://doi.org/10.1002/2211-5463.70265","url":null,"abstract":"<p><p>Ischemic heart disease remains a leading global cause of death. We investigated the cardioprotective effects of the selective cluster of differentiation-36 receptor (CD36) modulator azapeptide MPE-298 in a mouse model of myocardial ischemia-reperfusion. Given before reperfusion, a single intravenous dose of azapeptide MPE-298 reduced infarct size by 44% of the area-at-risk and transiently decreased left ventricular long-chain fatty acids (LCFA) accumulation, independently of saturation status. Metabolomic profiling identified changes in amino acids that may fuel the tricarboxylic acid cycle and provide substrates for glutathione-dependent antioxidant defense. Gene expression analysis showed transient modulation of oxidative stress and inflammation-associated genes in both heart and adipose tissue. Thus, we conclude that modulation of CD36 by azapeptide MPE-298 exhibits therapeutic potential for treating acute myocardial ischemia and reperfusion by supporting metabolic recovery and limiting excess LCFA uptake.</p>","PeriodicalId":12187,"journal":{"name":"FEBS Open Bio","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147835732","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}

{"title":"UiO-66 metal-organic frameworks in biomedicine: From structural tunability to bioimaging, photodiagnostics, and photodynamic cancer therapy.","authors":"Veronika Huntošová, Grigorii Rakhalskii, Miroslav Almáši","doi":"10.1002/2211-5463.70266","DOIUrl":"https://doi.org/10.1002/2211-5463.70266","url":null,"abstract":"<p><p>UiO-66-type zirconium metal-organic frameworks (MOFs) have emerged as robust and highly tunable nanoplatforms for biomedical applications owing to their permanent porosity, exceptional chemical stability, and versatile functionalization pathways. Here, we summarize recent advances in engineering UiO-66-based nanoparticles for drug delivery, multimodal bioimaging, photodiagnostics, and photodynamic therapy (PDT). Precise control over composition, surface chemistry, and postsynthetic modifications allow for high drug loading, stimuli-responsive release, and improved colloidal stability in biological environments. Strategies for active targeting using antibodies, peptides, aptamers, and small-molecule ligands significantly enhance tumor specificity. Furthermore, UiO-66 is increasingly used as a carrier for photosensitizers, contrast agents, and imaging probes, supporting multimodal fluorescence, CT, MRI, and photoacoustic imaging. The framework's ability to coordinate photosensitizers and modulate oxygen availability provides powerful opportunities for PDT, especially in hypoxic tumors. However, key challenges remain, including long-term biocompatibility, clearance, and scalable synthesis. Future prospects include programmable degradation, advanced surface architectures, biomimetic coatings, and multimodal phototheranostic platforms.</p>","PeriodicalId":12187,"journal":{"name":"FEBS Open Bio","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147835677","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}

{"title":"The role of lipid metabolism in neuronal senescence.","authors":"Dikaia Tsagkari, Eleftheria Panagiotidou, Nektarios Tavernarakis","doi":"10.1002/2211-5463.70181","DOIUrl":"10.1002/2211-5463.70181","url":null,"abstract":"<p><p>Senescence is a complex cellular state characterised by irreversible growth arrest and metabolic reprogramming. In neurons, senescence has been mainly observed in the context of ageing and age-related neurodegeneration. Lipid metabolism plays a critical role in cellular homeostasis, with emerging evidence suggesting that alterations in lipid species, including fatty acids, cholesterol, sphingolipids and phospholipids, fundamentally drive or contribute to the senescent phenotype in both neuronal and non-neuronal cells in the brain. Namely, changes in lipid species levels result in the accumulation of lipid droplets (LDs), leading to dysregulation of membrane dynamics, and in turn to the production of bioactive lipid mediators, which collectively shape the senescence-associated secretory phenotype (SASP) in the brain. In this review, we describe the cell type-specific patterns of lipid dysregulation in neurons, astrocytes, microglia and other glial cells during senescence, highlighting the role of key lipid species and their association with senescence markers and phenotypes. Furthermore, we discuss the bidirectional relationship between lipid metabolism and mitochondrial dysfunction in cellular senescence. We also examine the molecular mechanisms through which lipid metabolic pathways can orchestrate neural senescence and their contribution to ageing and age-related neurodegenerative disorders, such as Alzheimer's disease and Parkinson's disease. Finally, we review emerging therapeutic strategies targeting lipid metabolic pathways to modulate neural senescence and potentially ameliorate age-associated brain pathology.</p>","PeriodicalId":12187,"journal":{"name":"FEBS Open Bio","volume":" ","pages":"857-869"},"PeriodicalIF":2.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13145346/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145741738","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":"Anticancer sensitivities and biological characteristics of HCT116 cells resistant to the selective poly(ADP-ribose) glycohydrolase inhibitor.","authors":"Kaede Tsuda, Yoko Ogino, Akira Sato","doi":"10.1002/2211-5463.70178","DOIUrl":"10.1002/2211-5463.70178","url":null,"abstract":"<p><p>Poly(ADP-ribose) glycohydrolase (PARG) is a key enzyme involved in poly(ADP-ribose) (PAR) degradation and is considered a potential anticancer target. We previously investigated resistance mechanisms to the PARG inhibitor PDD00017273 in human colorectal cancer HCT116 cells and established an acquired PDD00017273-resistant HCT116R^PDD cell line. In this study, we analyzed the protein levels of enzymes associated with PAR metabolism in both parental HCT116 cells and resistant HCT116R^PDD cells using western blotting. PARG expression levels were similar between HCT116R^PDD and HCT116 cells. However, the levels of PARP1 and ARH3 were reduced in HCT116R^PDD cells compared to HCT116 cells. Nevertheless, intracellular PAR levels were elevated in HCT116R^PDD cells. Interestingly, HCT116R^PDD cells exhibited greater sensitivity to γ-ray irradiation and the nicotinamide phosphoribosyltransferase (NAMPT) inhibitor FK866 than the parental HCT116 cells, yet showed comparable sensitivity to 5-FU, cisplatin, and PARP inhibitors olaparib, talazoparib, and veliparib. Furthermore, we observed that HCT116R^PDD cells tended to maintain slightly higher levels of intracellular NAD⁺/NADH and ATP compared to parental HCT116 cells. These findings suggest that cancer cells employ a mechanism to regulate NAD⁺ and ATP levels, thereby avoiding cell death from intracellular PAR accumulation through coordinated PARP-PARG regulation.</p>","PeriodicalId":12187,"journal":{"name":"FEBS Open Bio","volume":" ","pages":"1020-1029"},"PeriodicalIF":2.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13145335/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145676705","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":"Targeting TNBC: core-shell polycationic polyurea dendrimers with inherent anticancer activity.","authors":"Adriana Cruz, Bruna Abreu, Cindy Mendes, Catarina Freitas-Dias, Filipe Gonçalves, Fernanda Silva, José Ramalho, Saudade André, Vasco D B Bonifácio, Jacinta Serpa","doi":"10.1002/2211-5463.70144","DOIUrl":"10.1002/2211-5463.70144","url":null,"abstract":"<p><p>Breast carcinoma (BC) is the most common malignancy in women, with triple-negative breast cancer (TNBC) making up 10-20% of cases. TNBC has limited targeted therapies and poor survival due to late diagnosis and metastasis. Dendrimers are precise nanostructures with a three-dimensional globular architecture designed to target the negatively charged membranes of cancer cells. This study evaluated the anticancer potential of two novel core-shell polycationic polyurea (PURE) dendrimers, PURE_G4-OEI₄₈ and PURE_G4-OCEI₂₄, targeting BC cell membranes. Both dendrimers selectively interacted with TNBC cells, inducing apoptosis, necroptosis, and ferroptosis. In vivo, they reduced tumor volume in HCC1806 xenografts, with PURE_G4-OEI₄₈ showing no toxicity, while PURE_G4-OCEI₂₄ induced mild hepatic toxicity. These results suggest PURE dendrimers are promising TNBC treatments, with further modifications needed to enhance efficacy and reduce toxicity.</p>","PeriodicalId":12187,"journal":{"name":"FEBS Open Bio","volume":" ","pages":"944-965"},"PeriodicalIF":2.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13145356/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147467412","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":"Cellular senescence: Molecular signatures and cellular remodeling.","authors":"Dimitris Kletsas","doi":"10.1002/2211-5463.70258","DOIUrl":"10.1002/2211-5463.70258","url":null,"abstract":"<p><p>Cellular senescence, a state of stable cell-cycle arrest accompanied by profound metabolic and secretory changes, has emerged as a central hallmark of aging and a key contributor to age-associated diseases. Despite the great progress in understanding the characteristics, the underlying molecular mechanisms, and the role of senescent cells in several pathologies, many crucial issues remain unresolved. In this 'In the Limelight' special issue of FEBS Open Bio, three review articles deal with the accurate detection of senescent cells in vivo, changes in intercompartmental communication in senescent cells, and the role of lipid metabolism in neuronal senescence.</p>","PeriodicalId":12187,"journal":{"name":"FEBS Open Bio","volume":"16 5","pages":"818-820"},"PeriodicalIF":2.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13145348/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147835735","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":"Pioglitazone plus (-)-epigallocatechin gallate: a novel approach to enhance osteogenic performance in aged bone marrow mesenchymal stem cells.","authors":"Ching-Yun Chen, Jia-Ci Jhang, Chun-Yi Peng, Quốc Cường Nguyễn, Feng-Huei Lin, Hung-Ming Wu, Shankung Lin","doi":"10.1002/2211-5463.70175","DOIUrl":"10.1002/2211-5463.70175","url":null,"abstract":"<p><p>Previously, we reported that netoglitazone, a thiadolidinedione, enhanced both adipogenesis and osteoblastogenesis, and that fatty acid synthase knockdown could selectively repress the adipogenic effect. Here, molecular evidence further demonstrated that pioglitazone enhanced osteoblastic differentiation at least through the protein kinase A/glycogen synthase kinase 3β signaling. (-)-Epigallocatechin gallate (EGCG), a fatty acid synthase inhibitor, selectively retained pioglitazone's pro-osteoblastic effect. Cultures of aged human bone marrow mesenchymal stem cells (bmMSCs) in alginate scaffolds revealed that pioglitazone and EGCG cooperatively enhanced osteoblastic differentiation, biological apatite production, and bone-like tissue maturation. These findings demonstrate that the combination of pioglitazone and EGCG is a promising strategy to enhance osteogenic performance in aged bmMSCs for the development of advanced bone graft materials.</p>","PeriodicalId":12187,"journal":{"name":"FEBS Open Bio","volume":" ","pages":"932-943"},"PeriodicalIF":2.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13145338/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145676740","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":"Overview of molecular signatures of senescence and associated resources: pros and cons.","authors":"Orestis A Ntintas, Sylvia Vagena, Pavlos Pantelis, Giorgos Theocharous, Russel Petty, Konstantinos Evangelou, Vassilis G Gorgoulis","doi":"10.1002/2211-5463.70134","DOIUrl":"10.1002/2211-5463.70134","url":null,"abstract":"<p><p>The accurate detection of cellular senescence is of paramount importance given its involvement in aging and age-related pathologies. Over the years, a variety of markers and methodologies have been developed to address this issue. Initially, wet-lab assays, dealing with single morphological traits and molecular markers, were implemented, though exhibiting technical challenges and ineffectiveness in identifying the inherently complex senescence phenotype. Recent developments led to the adoption of combinatorial approaches in the form of multimarker guideline algorithms, effectively bypassing these obstacles. Moreover, technological advances have facilitated the emergence of molecular signatures that exploit the large amount of data generated in the last decades to increase our awareness of this phenomenon and its consequences. Due to the overwhelming expansion of these signatures, we performed an analysis of their advantages and disadvantages, and here, we discuss future improvements.</p>","PeriodicalId":12187,"journal":{"name":"FEBS Open Bio","volume":" ","pages":"821-836"},"PeriodicalIF":2.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13145361/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145225353","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":"SIRT4 positively regulates autophagy via ULK1, but independently of HDAC6 and OPA1.","authors":"Isabell Lehmkuhl, Khawar Amin, Lydia Gabriel, Nils Hampel, Afshin Iram, Julia Hesse, Constanze Wiek, Jasmin Thuy Vy Nguyen, Helmut Hanenberg, Jürgen Scheller, M Reza Ahmadian, Björn Stork, Doreen M Floss, Roland P Piekorz","doi":"10.1002/2211-5463.70164","DOIUrl":"10.1002/2211-5463.70164","url":null,"abstract":"<p><p>The sirtuin SIRT4 has been implicated in the control of autophagy and mitochondrial quality control via mitophagy. However, the role of SIRT4 in regulating autophagy/mitophagy induced by different stressors is unclear. Here, we show that cells expressing SIRT4(H161Y), a catalytically inactive, dominant-negative mutant of SIRT4, fail to upregulate LC3B-II. These cells also exhibit a reduced autophagic flux upon treatment with different inducers of mitophagy/autophagy, that is, CoCl₂-triggered pseudohypoxia, CCCP (carbonyl cyanide 3-chlorophenylhydrazone)/oligomycin-mediated respiratory chain inhibition, or rapamycin treatment. Interestingly, SIRT4(H161Y) expression upregulated protein levels of HDAC6, which is involved in mitochondrial trafficking and autophagosome-lysosome fusion, and inhibited the conversion of OPA1-L to OPA1-S, which is associated with increased mitochondrial fusion and decreased mitophagy. Both HDAC6 and OPA1 are SIRT4 interactors. However, the pharmacological inhibition of HDAC6 using Tubacin or of OPA1 using MYLS22 did not restore the stress-induced upregulation of LC3B-II levels upon autophagy/mitophagy treatment in SIRT4(H161Y)-expressing cells. Remarkably, inhibition of autophagosome-lysosome fusion and thus disruption of late autophagic flux by BafA1 treatment also failed to restore LC3B-II levels upon autophagy/mitophagy treatment, suggesting an inhibitory effect of SIRT4(H161Y) on the initiation/early phase of autophagy. Consistent with this, we demonstrate that SIRT4(H161Y) promotes the phosphorylation of ULK1 at S638 and S758 (mTORC1 targets), both of which mediate an important inhibitory regulation of autophagy initiation. Thus, our data suggest a positive regulatory function of SIRT4 in the ULK1-dependent early regulation/initiation of stress-induced autophagic flux, presumably via modulation of AMPK/mTORC1 signaling.</p>","PeriodicalId":12187,"journal":{"name":"FEBS Open Bio","volume":" ","pages":"870-884"},"PeriodicalIF":2.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13145358/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145556659","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":"KLK7 overexpression promotes an aggressive phenotype and facilitates peritoneal dissemination in colorectal cancer cells.","authors":"Yosr Z Haffani, Tobias Dreyer, Meriem Naim, Rea Lo Dico, Natalia A Ignatenko, Viktor Magdolen, Dalila Darmoul","doi":"10.1002/2211-5463.70171","DOIUrl":"10.1002/2211-5463.70171","url":null,"abstract":"<p><p>Colorectal cancer (CRC) incidence and mortality continue to rise globally and new prognostic biomarkers are required for the development of targeted therapies. Several studies have suggested that tissue kallikrein-related peptidases (KLKs), including KLK7, contribute to tumorigenesis. We previously demonstrated KLK7's tumor-promoting role both in vitro and in vivo, but its role in CRC metastasis remains unclear. Here, using the Cancer Genome Atlas (TCGA), we confirmed that KLK7 expression is upregulated in advanced stages of CRC and its association with shorter progression-free survival (PFS) of patients. To further understand the role of KLK7 in CRC metastasis, we assessed its expression in ascites from CRC patients with peritoneal metastasis (PM), investigated cell behavior following KLK7 overexpression, and examined its role in metastasis using a mouse model. High KLK7 levels were found in malignant ascites, but not in benign ascites. In xenograft models, KLK7-overexpressing cells increased PM and exhibited higher Peritoneal Cancer Index (PCI) scores compared to controls. In vitro, KLK7 overexpression in HT29-D4 human colon cancer cells significantly enhanced cell proliferation, colony formation, migration, spheroid formation, and adhesion to extracellular matrix proteins. Additionally, KLK7 overexpression altered cell morphology, upregulated moesin (MSN) and integrin subunits, suggesting cytoskeletal remodeling and matrix interactions. Taken together, these findings suggest that KLK7 is a driver of CRC progression and could serve as a potential prognostic marker for aggressive forms of CRC.</p>","PeriodicalId":12187,"journal":{"name":"FEBS Open Bio","volume":" ","pages":"1000-1019"},"PeriodicalIF":2.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13145359/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145667858","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}