@article{%a1.%Y_267,

title = {Bi-allelic variants in FSD1L cause a neurodevelopmental disorder overlapping with L1 syndrome},

author = {Serpieri V and Vezain-Mouchard M and Orsi A and Lecointre M and Mazzotta C and Marguet F and Garbelli A and Marcorelles P and Celli L and Goldenberg A and De Mori R and Drouot N and Petrizzelli F and Janin F and Nicolas G and Smal N and Condoluci C and Marini C and Tran-Mau-Them F and Ruault V and Micalizzi A and Bione S and Mazza T and Pichiecchio A and Ginevrino M and Weckhuysen S and Bedois A and Desnous B and Hermitte L and Rabie G and Kanaan M and Gonzalez BJ and Sabbioneda S and Laquerrière A and Saugier-Veber P and Valente EM},

url = {https://www.sciencedirect.com/science/article/pii/S0002929726000364?via%3Dihub},

doi = {10.1016/j.ajhg.2026.01.014},

year  = {2026},

date = {2026-03-16},

journal = {American journal of human genetics},

volume = {113},

issue = {3},

pages = {600-615},

abstract = {Disruption of the complex processes underlying central nervous system development leads to a broad spectrum of brain malformations and neurodevelopmental disorders, often with a genetic cause. Here, we report bi-allelic pathogenic variants in fibronectin type III and SPRY domain-containing 1-like (FSD1L), encoding a protein of unknown function, in eleven individuals, including five fetuses from six unrelated families. The phenotype ranges from severe hydrocephalus, corpus callosum agenesis, and absent pyramid decussation to a neurodevelopmental syndrome characterized by severe intellectual disability, spastic tetraparesis, reduced vision, and epilepsy, associated with corpus callosum agenesis/hypoplasia, mild ventricular dilation, optic nerve hypoplasia, and white matter reduction. This phenotype closely resembles that observed in L1 syndrome, caused by pathogenic variants in L1CAM, encoding a neural adhesion molecule. The knockdown of Fsd1l in mouse embryos recapitulated the ventricular dilation observed in affected fetuses. Immunohistochemical studies in human control fetuses revealed that FSD1L localized to neurons with commissural fate and projection neurons during human development. Induced pluripotent stem cell (iPSC)-derived neural progenitor cells from affected individuals failed to differentiate into premature neurons and to properly form neurospheres while undergoing increased cell death. In neural progenitors, FSD1L localized with microtubules of the mitotic spindle during M phase and to the transition zone and along the axoneme of the primary cilium during interphase. In line with this, fibroblasts from affected individuals exhibited marked alterations of the mitotic spindle and reduced ciliogenesis and ciliary length compared to control cells. Our findings define FSD1L as a microtubule-associated protein implicated in neuronal differentiation, axon guidance, and fasciculation.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Y_266,

title = {Identification of 3-cyanoquinolines as broad-spectrum inhibitors of Monkeypox virus and other sexually transmitted pathogens},

author = {Martina MG and Mathez G and Rubini D and Valenti ME and Lachat P and Cristinelli S and Kebbi Beghdadi C and Carlen V and Crespan E and Bianchi E and Opota O and Greub G and Ciuffi A and Gouttenoire J and Radi M and Cagno V},

url = {https://www.sciencedirect.com/science/article/pii/S0753332226001125?via%3Dihub},

doi = {10.1016/j.biopha.2026.119080},

year  = {2026},

date = {2026-03-16},

journal = {Biomedecine & pharmacotherapie},

volume = {196},

pages = {119080},

abstract = {Sexually transmitted infections (STIs) remain a major global health concern, contributing significantly to morbidity and facilitating the co-transmission of other pathogens. Recent outbreaks of Monkeypox virus (MPXV) have further underscored the urgent need for broad-spectrum antiviral agents effective against emerging and re-emerging sexually transmissible viruses. We report here the design and synthesis of a series of 3-cyanoquinoline-based Src inhibitors to evaluate their antimicrobial efficacy against sexually transmitted pathogens. Among them, compound 7d demonstrated potent inhibitory activity against MPXV, Herpes simplex virus types 1 and 2, Hepatitis C virus, Human immunodeficiency virus, and Chlamydia trachomatis at non-toxic concentrations. Owing to its broad-spectrum profile and favorable cytotoxicity profile, compound 7d represents a promising candidate for development as a topical microbicide for the prevention and treatment of STIs. Interestingly, the screening also identified compound 7g, which, despite lacking Src inhibitory activity, exhibited selective antiviral activity against members of the Poxviridae family, suggesting the involvement of alternative host-dependent mechanisms that can be further exploited. Both compounds were non-toxic in relevant epithelial and mucosal tissue models. Collectively, these findings highlight the therapeutic potential of 3-cyanoquinoline derivatives as scaffolds for the development of novel broad-spectrum microbicides targeting a range of sexually transmitted pathogens.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Y_265,

title = {α-ketoglutarate/succinate ratio imbalance impairs thymine DNA glycosylase function and base excision repair process increasing susceptibility to pancreatic cancer},

author = {Malatesta S and Vigiano Benedetti V and Salviati E and Illi B and Manni I and Middonti E and Rampioni Vinciguerra GL and Licursi V and Troilo F and Colotti G and Cipolla L and Sabbioneda S and Perfetto L and Piaggio G and Bussolino F and Di Nicolantonio F and Campiglia P and Sommella EM and Mori M and Cencioni C and Spallotta F},

url = {https://www.nature.com/articles/s41419-026-08475-w},

doi = {10.1038/s41419-026-08475-w},

year  = {2026},

date = {2026-03-16},

journal = {Cell death and disease},

volume = {17},

issue = {1},

pages = {242},

abstract = {Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal cancer, with chronic metabolic disorders increasing risk and severity. Prolonged exposure to altered metabolism changes specific metabolite levels, impacting epigenetic landscape contributing neoplastic lesion acquisition. This study examines the interplay between metabolism and epigenetics in dysmetabolic-driven PDAC tumorigenesis, exploiting LSL-KrasG12D;PDX-1-Cre mice (KC mice) exposed to high-fat diet (HFD) and KRAS-mutated human pancreatic ductal epithelial (HPDE) cells. Untargeted metabolomics of HFD-fed KC pancreata reveals altered free fatty acid and elevated S-adenosyl methionine levels during tumorigenesis. Targeted metabolomics shows increased succinate alongside reduced α-ketoglutarate levels. This imbalance suggests an epigenetic derangement, targeting DNA methylation. In KRAS-mutated HPDE cells exposed to altered metabolism, the DNA demethylation complex of ten-to-eleven-translocation methylcytosine 1 and thymine DNA glycosylase (TDG) is disrupted, leading to iterative cytosine modification and apurinic/apyrimidinic (AP) site accumulation. Succinate directly binds TDG at arginine 275, hyperactivating it and increasing AP site formation. This alteration combined with the methylation-prone metabolic environment, impairs the base excision repair pathway by hypermethylating and downmodulating DNA ligases LIG1 and LIG3. This predisposes to genomic instability and pancreatic preneoplastic lesion development. These findings uncover a metabolic-epigenetic axis in dysmetabolic PDAC, highlighting how metabolite-driven epigenetic changes compromise DNA repair and drive tumorigenesis.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Y_264,

title = {The glycine-arginine-rich motif of 53BP1 modulates RNA interactions necessary for its liquid-liquid phase separation during DNA Damage Response},

author = {Terraneo F and Ceccon M and Sapkota O and Zheng T and Brizioli M and Dello Stritto A and Cummings S and Codispoti S and Ossolengo G and Orsenigo F and Magni S and Gottinger A and Mattevi A and Fuxreiter M and Fawzi NL and Lottersberger F and Giavazzi F and {d'Adda di Fagagna F}},

url = {https://www.biorxiv.org/content/10.64898/2026.01.30.702603v1},

doi = {10.64898/2026.01.30.702603},

year  = {2026},

date = {2026-03-16},

journal = {bioRxiv},

abstract = {The DNA damage response relies on the rapid assembly of repair factors into foci with properties of liquid-liquid phase separation, driven by de novo transcription of damage-induced RNAs. 53BP1 is a key component of these condensates, yet the molecular determinants driving this process remain unknown. Here, through computational, structural and in vitro approaches, we identify the oligomerization domain of 53BP1 and its glycine-arginine-rich (GAR) motif as crucial for RNA interactions and phase separation. Biophysical characterization reveals that 53BP1-RNA condensates can progressively mature into a more stable state, and that GAR mutants display aberrant material properties. Using a cellular model of telomere fusion events, we demonstrate that the GAR motif is essential for 53BP1-mediated DNA repair, which depends on the combined contributions of RNA binding and appropriate condensate biophysical properties. Therefore, RNA-driven 53BP1 condensation is functionally required to maintain genome integrity.},

keywords = {},

pubstate = {forthcoming},

tppubtype = {article}

}

@article{%a1.%Y_263,

title = {Autofluorescence and Fourier transform infrared analyses trace dietary fluorophores and reveal plastic contamination in the gut of mosquito larvae},

author = {Soldano S and Weththimuni ML and Oldani A and Girella A and Moyano A and Croce AC and Licchelli M and Gomulski LM and Scolari F},

url = {https://www.nature.com/articles/s41598-026-38938-1},

doi = {10.1038/s41598-026-38938-1},

year  = {2026},

date = {2026-03-16},

journal = {Scientific reports},

abstract = {No abstract available},

keywords = {},

pubstate = {forthcoming},

tppubtype = {article}

}

@article{%a1.%Y_262,

title = {Molecular evolution of animal aging},

author = {Nussey DH and {d'Adda di Fagagna F} and Bardin AJ and Blau H and Brunet A and Bulavin DV and Guo L and Hara E and Junker JP and Gorbunova V and Mittelbrunn M and Rera M and Reznick J and Seluanov A and Schumacher B and Teeling EC and Valenzano DR and Ye J and Yun MH and Garinis GA and Gilson E},

url = {https://link.springer.com/article/10.1038/s44318-026-00725-z},

doi = {10.1038/s44318-026-00725-z},

year  = {2026},

date = {2026-03-16},

journal = {EMBO journal},

abstract = {Comparative biology plays a crucial role in uncovering fundamental biological mechanisms and providing evolutionary models for their variation. This approach is particularly valuable for studying aging, given the remarkable diversity in aging trajectories across the tree of life. Many evolutionary theories of aging were proposed well before the discovery of the molecular mechanisms involved, and they remain largely theoretical. Moreover, the growing number of model organisms and the expanding array of experimental and theoretical approaches used to study aging have often remained compartmentalized. As a result, integrating these diverse insights into a unified framework has become increasingly important. As a step toward this goal, this field perspective outlines general biological mechanisms that help explain the variability in aging patterns and longevity across the animal kingdom.},

keywords = {},

pubstate = {forthcoming},

tppubtype = {article}

}

@article{%a1.%Y_261,

title = {DNA double-strand break response at a glance},

author = {Esposito F and Francia S},

url = {https://journals.biologists.com/jcs/article-abstract/139/4/jcs263423/370955/DNA-double-strand-break-response-at-a-glance?redirectedFrom=fulltext},

doi = {10.1242/jcs.263423},

year  = {2026},

date = {2026-03-16},

urldate = {2026-03-16},

journal = {Journal of cell science},

volume = {139},

issue = {4},

pages = {jcs263423},

abstract = {DNA double-strand breaks (DSBs) are among the most cytotoxic and most frequent lesions that arise in the mammalian genome; they occur as a result of both external insults and internal metabolic activities. Failures in damage signalling and repair of DSBs can result in permanent cell cycle arrest, cellular senescence, cell death or the accumulation of mutations and genomic instability - events that ultimately disrupt tissue homeostasis. To reduce these detrimental outcomes, cells have evolved a sophisticated and tightly coordinated network of mechanisms for detecting, signalling and repairing DNA lesions, collectively known as the DNA damage response (DDR). Repair occurs within the chromatin landscape, with DDR sensors, mediators, signalling kinases and ubiquitin ligases rapidly recruited to the site of damage. Simultaneously, local chromatin modifications and remodelling take place, which also modulate local transcriptional activity. More complex chromatin dynamics are subsequently orchestrated within the three-dimensional nuclear space - persistent DSBs are actively relocated to specialized nuclear domains and chromatin compartments undergo spatial reorganization to facilitate efficient repair. In this Cell Science at a Glance article and the accompanying poster, we explore the interplay between local and global chromatin dynamics that coordinate DSB repair and preserve genome integrity within the context of a highly dynamic epigenome.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Y_260,

title = {Complex I Modulator BI4500 Reduces MASH by Limiting Oxidative Stress and Reprogramming Lipid Metabolism via AMPK in MCD Rats},

author = {Di Pasqua LG and Lotti S and Trucchi M and Palladini G and Croce AC and Protopapa F and Feletti F and Kauschke SG and Sun P and Vairetti M and Ferrigno A},

url = {https://www.mdpi.com/2076-3921/15/1/82},

doi = {10.3390/antiox15010082},

year  = {2026},

date = {2026-02-04},

journal = {Antioxidants},

volume = {15},

issue = {1},

abstract = {Background: Metabolic-dysfunction-associated steatotic liver disease (MASLD) is a multifactorial liver disease in which mitochondrial dysfunction, oxidative stress, and inflammation play key roles in driving the progression toward metabolic dysfunction-associated steatohepatitis (MASH) and hepatocellular carcinoma (HCC). Dysfunctional mitochondria generate excess reactive oxygen species (ROS), impair antioxidant defenses, activate pro-inflammatory pathways and hepatic stellate cells, and perpetuate liver injury. Mitochondrial Complex I is a major ROS source, particularly under conditions of dysregulated energy metabolism. Since Complex I inhibition by metformin was shown to reduce ROS and activate the adenosine monophosphate-activated protein kinase (AMPK), this study aimed to evaluate whether a novel Complex I Modulator (CIM, BI4500) could attenuate oxidative stress, inflammation, and consequently reduce lipid accumulation and fibrosis in a methionine- and choline-deficient diet (MCD)-fed rat model of MASH. Methods: Rats were fed an MCD or an isocaloric control diet for six weeks. From week four, animals received daily oral treatment with CIM (10 mg/kg) or vehicle (Natrosol). At the endpoint, liver tissue was collected for histological, biochemical, and molecular analyses. Lipid droplet area, inflammatory infiltration, and collagen deposition were evaluated on tissue sections; total lipid content and oxidative stress markers were assessed in homogenates and isolated mitochondria. Molecular pathways related to oxidative stress, lipid metabolism, and fibrosis were assessed at protein and mRNA levels. Results: CIM treatment significantly reduced oxidative stress (ROS, lipid peroxidation, nitrogen species), promoting AMPK activation and metabolic reprogramming. This included increased expression of peroxisome proliferator-activated receptor alpha (PPAR-α) and its target genes, and decreased sterol regulatory element binding protein-1c (SREBP-1c)-driven lipogenesis. These changes halted fibrosis progression, as confirmed by Picro-Sirius Red staining and fibrosis markers.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Y_259,

title = {Dissecting the Interaction Domains of SARS-CoV-2 Nucleocapsid Protein and Human RNA Helicase DDX3X and Search for Potential Inhibitors},

author = {Lodola C and Pallotta MM and Manetti F and Governa P and Crespan E and Maga G and Secchi M},

url = {https://www.mdpi.com/1422-0067/27/2/672},

doi = {10.3390/ijms27020672},

year  = {2026},

date = {2026-02-04},

urldate = {2026-02-04},

journal = {International journal of molecular sciences},

volume = {27},

issue = {2},

pages = {672},

abstract = {The SARS-CoV-2 nucleocapsid protein (Np) plays multifunctional roles in the viral life cycle. By interacting with host cellular proteins, Np regulates viral RNA transcription, replication, and immune evasion. It controls genome packaging and counteracts host RNA interference mediated antiviral responses through its RNA binding activity. Previous studies revealed a physical interaction between Np and DDX3X, a human DEAD-box RNA helicase that facilitates the replication of several viruses. This interaction enhances Np affinity for double-stranded RNA and inhibits DDX3X helicase activity. Since Np-RNA binding activity promotes ribonucleoprotein complex formation, targeting this interaction is a promising antiviral strategy. We generated truncated protein variants to define interaction regions between Np and DDX3X. Using AlphaFold modelling, we identified RecA2 as the key DDX3X domain involved in Np binding. Finally, to disrupt Np-RNA complex formation, we screened a small molecule library of putative binders of Np N-terminal region and identified two candidate inhibitors for further development.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Y_258,

title = {Daxx-Dependent H3.3 Deposition Promotes Double-Strand Breaks Repair by Homologous Recombination},

author = {Zannini L and Aliprandi S and Delia D and Buscemi G},

url = {https://www.mdpi.com/2073-4409/15/2/162},

doi = {10.3390/cells15020162},

year  = {2026},

date = {2026-02-04},

journal = {Cells},

volume = {15},

number = {162},

issue = {2},

abstract = {DNA double-strand breaks (DSBs) can be induced by cellular byproducts or genotoxic agents. Improper processing of these lesions leads to increased genome instability, which constitutes a hallmark of pathological conditions and fuels carcinogenesis. DSBs are primarily repaired by homologous recombination (HR) and non-homologous end joining (NHEJ) and the proper balance between these two pathways is finely modulated by specific molecular events. Here, we report that the histone chaperone DAXX plays a fundamental role in the response to DSBs. Indeed, in human cells, DSBs induce ATM/ATR-dependent phosphorylation of DAXX on serine 424 and 712 and promote its binding to chromatin and the deposition of the histone variant H3.3 in proximity to DNA breaks. Enrichment of H3.3 at DSBs promotes 53BP1 recruitment to these lesions and the repair of DNA breaks by HR pathways. Moreover, H3.3-specific post translational modifications, particularly K36 tri-methylation, play a key role in these processes. Altogether, these findings indicate that DAXX and H3.3 mutations may contribute to tumorigenesis-enhancing genome instability.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Y_257,

title = {Analysis of BAL extracellular vesicles unveils NF-κB activation at the onset of chronic lung allograft dysfunction},

author = {Storaci AM and de Filippo MR and Franzi S and Mansour N and Lopez G and Molisso MT and Zadra G and Brevi M and Gianazza E and Banfi C and Bianchi C and Garulli G and Mendogni P and Nosotti M and Blasi F and Morlacchi LC and Palleschi A and Vaira V},

url = {https://portlandpress.com/clinsci/article-abstract/140/1/97/237053/Analysis-of-BAL-extracellular-vesicles-unveils-NF?redirectedFrom=fulltext},

doi = {10.1042/CS20258651},

year  = {2026},

date = {2026-02-04},

journal = {Clinical science},

volume = {140},

issue = {1},

pages = {97-114},

abstract = {The onset of chronic lung allograft dysfunction (CLAD) represents the greatest long-term challenge in lung transplantation (LT). Here we aimed to identify early molecular signals of CLAD by analyzing the effects of bronchoalveolar lavage (BAL)-derived extracellular vesicles (EVs) on airway cells and validating these findings in patient lung tissues. In our BAL biobank, we identified 13 LT patients with a BAL sample at CLAD diagnosis and 13 patients with a stable graft function and a BAL sample obtained at least 12 months post LT (Ctrl). All patients were then followed for at least 18 months. EVs were isolated, immunophenotyped, and co-cultured with airway cells. The cells' transcriptome and proteome were profiled. Selected targets were validated by immunohistochemistry. Logistic regression and survival analyses were performed for prediction of CLAD progression. During follow-up, 7 CLAD patients experienced allograft dysfunction aggravation, and one control developed CLAD. CLAD patients showed more EVs originating from epithelial cells and leukocytes than stable LT recipients. Exposure of airway cells to CLAD-EVs led to the up-regulation of p70S6K and canonical NF-κB signaling, altering their intracellular and extracellular proteome. Activation of NF-κB was also detected at the onset of CLAD in transbronchial biopsies and BAL cytology, and it persisted throughout the progression to end-stage CLAD. RelA overexpression was associated with poorer graft performance and worse outcomes. RelA-driven NF-κB activation is a key factor in the development of CLAD by promoting persistent inflammation. This pathway may be a promising therapeutic target to improve long-term graft survival after LT.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Y_256,

title = {Targeting metabolic vulnerabilities: REV-ERB agonist SR9009 potentiates sorafenib efficacy in liver cancer},

author = {Sabbioni S and Guerriero P and Shankaraiah RC and Masatti L and Michilli A and Bassi C and D'Abundo L and Moshiri F and De Siena B and Simoni E and Astolfi L and Gramantieri L and Roncarati R and Elamin BK and Bonora M and Pinton P and Croce CM and Negrini M and Callegari E},

url = {https://www.nature.com/articles/s41420-026-02940-3},

doi = {10.1038/s41420-026-02940-3},

year  = {2026},

date = {2026-02-04},

journal = {Cell death & differentiation},

abstract = {Hepatocellular carcinoma (HCC) is one of the most common cancers and the third leading cause of cancer-related death worldwide. The prognosis is poor, with a median survival of 12-15 months in patients with advanced-stage disease. Early diagnosis and the development of new, more effective therapeutic strategies are needed to address the challenges posed by this malignancy. Although immune checkpoint inhibitors have replaced multikinase inhibitors as first-line therapy, sorafenib continues to represent a valuable option for patients with contraindications to newer treatments. Based on genome-wide RNA-seq analysis, which identified mitochondrial oxidative phosphorylation (OxPhos) and Hmox1 upregulation as potential pro-survival mechanisms in sorafenib-resistant cells, we investigated whether SR9009, a synthetic agonist of the nuclear receptor REV-ERBα/β, heme competitor, and inhibitor of mitochondrial respiration, could enhance the antitumor efficacy of sorafenib in liver cancer models. Co-treatment with SR9009 and sorafenib significantly enhanced cytotoxic effects in both mouse and human liver cancer cells. This synergistic activity was associated with increased levels of free heme and a complete inhibition of mitochondrial OxPhos. In vivo xenograft studies confirmed that the combination was effective even in sorafenib-resistant tumors. Furthermore, in a N-Nitrosodiethylamine (DEN)-induced HCC model, the combination therapy led to a reduction in size in over 90% of tumor nodules, representing a significant improvement over sorafenib alone. The combination was well tolerated, with no evident signs of acute toxicity. These findings support the concept that the efficacy of anticancer therapies can be enhanced by targeting the metabolic adaptations that tumor cells rely on for survival. Combining sorafenib with agents like SR9009, that disrupt metabolic homeostasis, may offer a promising strategy for treating advanced HCC.},

keywords = {},

pubstate = {forthcoming},

tppubtype = {article}

}

@article{%a1.%Y_255,

title = {RNA polymerase II degradation triggered by DNA repair occurs in trans and independently of how the lesion is recognized},

author = {Choudhary R and Munoz JC and Beckerman I and Rebottaro ML and Bastianello G and Bouvier LA and Foiani M and Munoz MJ},

url = {https://pmc.ncbi.nlm.nih.gov/articles/PMC12781871/},

doi = {10.1093/nar/gkaf1416},

year  = {2026},

date = {2026-02-04},

journal = {Nucleic acids research},

volume = {54},

issue = {1},

abstract = {In response to DNA damage, RPB1, the catalytic subunit of RNA Polymerase II (RNAPII), is degraded by the ubiquitin-proteasome system. Degradation models only consider transcriptionally engaged molecules, where a stalled RNAPII complex functions as a lesion-recognition factor, and its RPB1 subunit is proposed to be subsequently degraded to facilitate access of lesion-processing nucleotide excision repair (NER) factors. This transcription-coupled repair is complemented by the global genome repair (GG-NER) system, where lesions are recognized by the XPC and DDB2 factors. Here, we show that RPB1 degradation is controlled in trans by a pathway that depends on lesion processing by NER, irrespectively of whether the lesion is recognized by RNAPII itself or by XPC-DDB2. Incomplete repair due to absence of lesion-processing factors (XPA, XPB, XPD, XPF, or XPG) enhances RPB1 degradation, indicating that the signal controlling RPB1 abundance is started by lesion recognition and continues until DNA repair is completed. Consistent with an in trans mechanism, damage-induced RPB1 degradation is not restricted to active nor phosphorylated RPB1 molecules and depends on Cullin-RING ubiquitin ligases. These findings uncover a repair-dependent mechanism controlling RPB1 levels and provide a rationale for the control of gene expression under stress, where more damage implies more repair and less RPB1 levels, hence restricting RNAPII activity.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Y_254,

title = {Targeting HGF/MET and CXCL1/CXCR2 axes bypasses resistance to KRASG12C inhibitors in NSCLC},

author = {Cavazzoni A and Pagano Mariano M and Palladini A and Digiacomo G and La Monica S and Bonelli M and Galetti M and Pace I and Roncarati R and Giovannetti E and Aretini P and Minari R and Treccani M and Pluchino M and Lagrasta CA and Angelicola S and Mazzaschi G and Bordi P and Gelsomino F and Agustoni F and Petronini PG and Tiseo M and Ferracin M and Alfieri R},

url = {https://www.sciencedirect.com/science/article/pii/S0169500226000346?via%3Dihub},

doi = {10.1016/j.lungcan.2026.108939},

year  = {2026},

date = {2026-02-04},

urldate = {2026-02-04},

journal = {Lung Cancer},

volume = {213},

pages = {108939},

abstract = {Background: Resistance to KRASG12C inhibitors sotorasib and adagrasib, approved for KRASG12C-mutant advanced Non-Small Cell Lung Cancer (NSCLC), involves multiple subclonal events, raising significant concerns about overcoming the resistant phenotype. Cytokines, chemokines, and growth factors are key mediators of drug resistance and targeting their signaling pathways is an emerging strategy in cancer therapy. Methods: We generated cell clones from KRASG12C-mutated NSCLC cells treated with KRAS inhibitors and cell cultures from a sotorasib-resistant patient-derived xenograft (PDX). Gene mutations and changes in gene expression were evaluated using NGS, RNAseq. The mRNA and protein levels encoded by the Hepatocyte Growth Factor (HGF) and CXCL1 genes were quantified using RT-PCR and ELISA assay. The effect of drug combination was obtained by the Sulforhodamine-B assay and analyzed by Combenefit Software. Cell death was detected by Annexin-V assay. Cell signaling and epithelial-to-mesenchymal transition were evaluated by Western blotting. Results: NSCLC cell clones and PDX cell cultures with acquired and intrinsic resistance to KRASG12C inhibitors exhibited elevated levels of CXCL1 and HGF expression and secretion, with activation of CXCR2 and c-MET signalling pathways. The combination of CXCR2 and c-MET inhibitors led to synergistic inhibition of cell growth and reduced cell viability by inhibiting the ERK1/2 and AKT signalling pathways. This combination also reversed EMT and induced apoptosis in sotorasib- and adagrasib-resistant clones, regardless of the genetic alterations responsible for resistance. Conclusions: CXCL1/CXCR2 and HGF/c-MET may represent compensatory pathways that sustain proliferation and survival in resistance to KRASG12C inhibitors. The simultaneous blockade of these signals may offer a novel strategy for bypassing resistance.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Y_253,

title = {Unusual Disease-Progression in Two Siblings With Xeroderma Pigmentosum Group G},

author = {Botta E and Fawcett H and Orioli D and Fassihi H and Lehmann AR},

url = {https://onlinelibrary.wiley.com/doi/10.1111/cge.70129},

doi = {10.1111/cge.70129},

year  = {2026},

date = {2026-02-04},

journal = {Clinical genetics},

abstract = {Protein truncation mutations in the gene for XPG nuclease cause a very severe clinical phenotype. Two siblings have splicing mutations, which result in in-frame deletions and a less severe phenotype.},

keywords = {},

pubstate = {forthcoming},

tppubtype = {article}

}

@article{%a1.%Y_238,

title = {DBR1 and the RNAopathy Landscape of Trichothiodystrophy},

author = {Veniali G and Lanzafame M},

url = {https://www.sciencedirect.com/science/article/abs/pii/S0022202X25023139?via%3Dihub},

doi = {10.1016/j.jid.2025.07.011},

year  = {2026},

date = {2026-01-05},

urldate = {2025-10-10},

journal = {Journal of investigative dermatology},

volume = {146},

issue = {2},

pages = {298-301},

abstract = {not available - Commentary to "RNA Lariat-Debranching Enzyme (DBR1) Variations in Sabinas Brittle Hair Syndrome Form of Trichothiodystrophy: A Trichothiodystrophy-Causing Gene" Sikandar G. Khan, Wenelia Baghoomian,  Christiane Kuschal-Tauzon, Deborah Tamura, Maxwell P. Lee, John J. DiGiovanna, Rodrigo Cepeda-Valdes, Julio Salas-Alanis, Kenneth H. Kraemer (DOI: https://doi.org/10.1016/j.jid.2025.06.1591)},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Y_247,

title = {Farnesoid X Receptor Agonist INT-787 Inhibits Hepatic Mitochondrial Dysfunction in a Diet-Induced ob/ob Mouse Model of MASH},

author = {Di Pasqua LG and Palladini G and Croce AC and Milanesi G and Cavallo M and Adorini L and Ferrigno A and Vairetti M},

url = {https://www.mdpi.com/1422-0067/26/22/11023},

doi = {10.3390/ijms262211023},

year  = {2025},

date = {2025-12-22},

urldate = {2025-12-22},

journal = {International journal of molecular sciences},

volume = {26},

issue = {2},

pages = {11023},

abstract = {This study evaluated the protective role of farnesoid-X-receptor (FXR) agonist INT-787 in the control of mitochondrial changes using a metabolic dysfunction-associated steatohepatitis (MASH) model. Lep-ob/ob mice were fed a control diet (CD) for 21 weeks (wks), or a high-fat diet (HFD) for 9 or 21 wks; in the 21 wk HFD groups, INT-787 (30 mg/kg/day) dosed via HFD admixture was added. The hepatic ATP, ROS, GSH and MIC19, which stabilizes the structure of inner mitochondrial membrane (IMM), were quantified. Transmission electron microscopy (TEM) analysis was also performed. INT-787 increased hepatic ATP, which was downregulated after HFD 9 and 21 wks. Hepatic ROS increased and GSH decreased after 21 wks and were recovered by INT-787. MIC19 mRNA level decreased after HFD 21 wks, and it was completely restored after INT-787 administration. TEM analysis showed that INT-787 reverted the mitochondrial alterations as documented by restored mitochondrial length, number of mitochondrial cristae junctions (CJs), and distance between endoplasmic reticulum (ER) and outer mitochondrial membrane (OMM) when compared with HFD groups. These results underline the involvement of the FXR pathway in the control of mitochondrial damage, thus revealing a previously undiscovered mechanism mediated by FXR activation: the upregulation of IMM protein MIC19, which is essential for maintaining cristae integrity and mitochondrial function.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Y_248,

title = {CAPE Derivatives as Potent Agents for Induction of Osteogenic Differentiation in DPSCs and Biomaterial Development},

author = {Balaha M and De Filippis B and Rapino M and Kazimierczak P and Przekora A and Esmail T and Toto EC and Petrucci G and Canal C and Cataldi A and di Giacomo V},

url = {https://www.mdpi.com/2227-9059/13/12/3039},

doi = {10.3390/biomedicines13123039},

year  = {2025},

date = {2025-12-20},

journal = {Biomedicines},

volume = {13},

issue = {12},

pages = {3039},

abstract = {Objectives: Bone defects, resulting from many causes, represent a challenge in maxillofacial and orthopedic surgery. Regenerative medicine offers promising strategies by introducing exogenous materials to modify the tissue environment and modulate the body's natural healing mechanisms. Dental pulp stem cells (DPSCs) are considered an effective source for tissue repair. Small molecules such as caffeic acid phenethyl ester (CAPE), although having promising effects in promoting bone regeneration, are characterized by low chemical stability, which impairs their clinical application. This study aimed to investigate the bone regenerative capability of four CAPE derivatives, recently synthesized in our laboratory and selected based on previous studies. Methods: DPSCs were induced to osteogenic differentiation in the presence of these compounds (0-5 μM), and cell viability, matrix deposition, alkaline phosphatase activity, and osteogenic marker gene expression were evaluated. In addition, bone biomaterials composed of a chitosan/agarose matrix reinforced with nanohydroxyapatite and enriched with these CAPE derivatives were fabricated and assessed for cytotoxicity and cell adhesion. Results: Two of the tested compounds effectively enhanced DPSC differentiation toward the osteogenic lineage. The fabricated bone biomaterials showed no cytotoxicity and supported cell adhesion. Furthermore, these compounds demonstrated stability under various conditions, confirming their suitability for incorporation into bone biomaterials. Conclusions: The tested CAPE derivatives exhibit promising osteoinductive properties and stability, offering a valid alternative to traditional therapeutic strategies in regenerative medicine.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Y,

title = {DROSHA, DICER, and damage-induced long ncRNA control BMI1-dependent transcriptional repression at DNA double-strand break},

author = {Esposito F and Capozzo I and Riccardi A and Gioia U and Modafferi S and Manfredi L and Colantoni A and Tavella S and Cabrini M and Iannelli F and di Lillo A and {d'Adda di Fagagna F} and Francia S},

url = {https://www.sciencedirect.com/science/article/pii/S2211124725013774?via%3Dihub},

doi = {10.1016/j.celrep.2025.116605},

year  = {2025},

date = {2025-12-16},

urldate = {2025-12-16},

journal = {Cell reports},

volume = {44},

issue = {12},

pages = {116605},

abstract = {The activation of the DNA-damage response (DDR) enforces the transcriptional silencing of genes near DNA double-strand breaks (DSBs), a process called DSB-induced silencing in cis (DISC). DISC involves the kinase ATM and the polycomb repressive complex 1 (PRC1) component BMI1. Conversely, DSBs also trigger transcription of damage-induced long non-coding RNAs (dilncRNAs) in an MRE11-RAD50-NBS1 (MRN)-complex-dependent manner. MRN recruits the ribonuclease DROSHA, which, along with DICER, enhances DDR signaling and repair. We show that dilncRNAs, DROSHA, and DICER regulate DISC. MRN or ATM inhibition disrupts DISC, while enoxacin, a DICER activator, restores it even without ATM activity. Mechanistically, DROSHA and DICER enable BMI1 recruitment and H2A-K119 ubiquitination at DSBs. BMI1 interacts with DROSHA and dilncRNAs in a DICER-dependent manner. Blocking dilncRNAs by antisense oligonucleotide and Cas13 reduces BMI1 recruitment and DISC. We propose that DROSHA, DICER, and dilncRNAs mediate DISC by promoting PRC1 recruitment and chromatin modification at DSBs.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Y_250,

title = {Endosymbiont hijacking of acylcarnitines regulates insect vector fecundity by suppressing the viability of stored sperm},

author = {Weiss BL and Gstöttenmayer F and Awuoche E and Smallenberger GM and Attardo GM and Scolari F and Koch RT and Bruzzese DJ and Echodu R and Opiro R and Malacrida A and Abd-Alla AMM and Aksoy S},

url = {https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1011974},

doi = {10.1371/journal.pgen.1011974},

year  = {2025},

date = {2025-12-16},

journal = {PLoS genetics},

volume = {21},

issue = {12},

pages = {e1011974},

abstract = {Competition between insects and their endosymbiotic bacteria for environmentally limited nutrients can compromise the fitness of both organisms. Tsetse flies, the vectors of pathogenic African trypanosomes, harbor a species and population-specific consortium of vertically transmitted endosymbiotic bacteria that range on the functional spectrum from mutualistic to parasitic. Tsetse's indigenous microbiota can include a member of the genus Spiroplasma, and infection with this bacterium causes fecundity-reducing phenotypes in the fly that include a prolonged gonotrophic cycle and a reduction in the motility of stored spermatozoa post-copulation. Herein we demonstrate that Spiroplasma and tsetse spermatozoa compete for fly-derived acylcarnitines, which in other bacteria and animals are used to maintain cell membranes and produce energy. The fat body of mated female flies increases acylcarnitine production in response to infection with Spiroplasma. Additionally, their spermathecae (sperm storage organs), and likely the sperm within, up-regulate expression of carnitine O-palmitoyltransferase-1, which is indicative of increased acylcarnitine metabolism and thus increased energy demand and energy production in this organ. These compensatory measures are insufficient to rescue the motility defect of spermatozoa stored in the spermathecae of Spiroplasma-infected females and thus results in reduced fly fecundity. Tsetse's taxonomically simple and highly tractable indigenous microbiota make the fly an efficient model system for studying the biological processes that facilitate the maintenance of bacterial endosymbioses, and how these relationships impact conserved mechanisms (mammalian spermatozoa also use acylcarnitines as an energy source) that regulated animal host fecundity. In the case of insect pests and vectors, a better understanding of the metabolic mechanisms that underlie these associations can lead to the development of novel control strategies.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Y,

title = {Aging well in an aging society: Italy at the forefront of global aging and the Age-It Research Program},

author = {Vignoli D and Albertini M and Chiatti C and Aimaretti G and Boccuzzo G and Boffo V and Brugiavini A and Cavallo F and Cenci S and Cherubini A and Cincotti F and {d'Adda di Fagagna F} and Ferrarese C and Galasso V and Galeotti E and Graziani A and Iaccarino G and Lattanzio F and Lucifora C and Mezzanzanica M and Passarino G and Paterno A and Prati S and Rumiati RI and Sandri M and Tomassini C and Torbica A and Ungar A and Petrucci A},

url = {https://pmc.ncbi.nlm.nih.gov/articles/PMC12736989/},

doi = {10.1093/geronb/gbaf219},

year  = {2025},

date = {2025-12-16},

urldate = {2025-12-16},

journal = {Journals of gerontology. Series B, Psychological sciences and social sciences},

volume = {80},

issue = {suppl. 2},

pages = {S99-S109},

abstract = {Objectives: Italy, one of the world's super-aged societies, faces profound demographic transformations amid relevant regional disparities in sociodemographic trends, institutional structures, and economic conditions. These features make it an ideal laboratory to study both the challenges and opportunities of population aging. This article introduces Age-It, a Research Program designed to leverage Italy's position at the forefront of global aging to advance transdisciplinary research and inform evidence-based policies and practices on aging. Methods: Age-It adopts a life course perspective encompassing individual, family, and societal levels. It conceptualizes "aging well" as the outcome of multi-agent, multi-context processes unfolding from early life through old age. Furthermore, Age-It moves beyond a multidisciplinary approach by fostering true cross-fertilization between biomedical, sociodemographic, and technological sciences. Structured as an umbrella initiative, the program brings together multiple interlinked projects that address diverse dimensions of aging through transdisciplinary and collaborative research. Results: The program addresses key limitations in Italy's current aging research and policy landscape: fragmented data, disciplinary silos, and weak connections between research and policymaking. By integrating biomedical, technological, and socioeconomic perspectives into structured, theory-driven research centers (Spokes), Age-It provides a coordinated and innovative platform for studying aging. Discussion: Leveraging Italy's unique demographic profile and internal heterogeneity, Age-It promotes sustainable aging by harnessing the opportunities embedded in demographic change. The program ranges from the biology of aging to mental and physical health prevention, long-term care, labor market dynamics, and social participation-ultimately aiming to reshape how aging is perceived and managed in aging societies.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Y_249,

title = {Tendon Dysfunction in Collagen VI-Related Myopathies: Novel Mechanistic Insights with Therapeutic Potential},

author = {Sabatell P and Di Martino A and Faldini C and Bonaldo P and Merlini L and Cenni V},

url = {https://www.mdpi.com/1422-0067/26/24/12014},

doi = {10.3390/ijms262412014},

year  = {2025},

date = {2025-12-16},

journal = {International journal of molecular sciences},

volume = {26},

issue = {24},

pages = {12014},

abstract = {Collagen VI-related myopathies (COL6-RM) encompass a spectrum of disorders characterized by muscle weakness, joint contractures, and connective tissue abnormalities resulting from mutations in the collagen VI genes. While muscle pathology has been extensively studied, tendon dysfunction has emerged as a critical yet underexplored contributor to disease severity, particularly in the development of joint contractures. Tendons from patients and animal models show disrupted collagen fibrillogenesis, altered extracellular matrix (ECM) composition, and impaired cellular mechanotransduction. Various defects in ECM remodeling pathways further exacerbate tendon pathology. Importantly, current clinical management remains limited to orthopedic interventions with modest outcomes, and targeted pharmacological strategies or gene-editing therapies are not yet available for clinical application. Therefore, understanding the basic pathogenic mechanisms underlying tendon dysfunction is essential for identifying novel therapeutic targets. This review provides a comprehensive synthesis of current understanding and recent advances concerning the role of mutated collagen VI in cellular and molecular mechanisms underlying tendon dysfunction. Emphasis is placed on the role of mutated collagen VI in the modulation of key signaling pathways related to mechanotransduction and primary cilium function in COL6-RM. By discussing these multifaceted contributions to disease pathogenesis, this review outlines future research directions in the field and highlights potential pathways for targeted therapeutic interventions.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Y_246,

title = {The E3 ligase RNF32 controls the IκB kinase complex and NF-κB signaling in intestinal stem cells},

author = {Lauriola A and Enrique Steinberg JH and Sarubo M and Maspero E and Rossi FA and Mouri Y and Pedretti M and Hajisadeghian M and Taibi V and Vettori A and Vitulo N and Assfalg M and D'Onofrio M and Rossi M and Yasue A and Astegno A and Polo S and Santi S and Kudo Y and Guardavaccaro D



},

url = {https://www.sciencedirect.com/science/article/pii/S1097276525008226?via%3Dihub},

doi = {10.1016/j.molcel.2025.10.005},

year  = {2025},

date = {2025-11-19},

urldate = {2025-11-19},

journal = {Molecular cell},

volume = {85},

issue = {22},

pages = {4254-4267},

abstract = {Nuclear factor κB (NF-κB) signaling is a central pathway regulating a plethora of cellular functions. Here, we find that RNF32, a RING E3 ubiquitin ligase whose expression is enriched in murine intestinal stem cells, regulates the activity of the IκB kinase (IKK) complex, the signal integration hub for NF-κB activation. The E3 ligase activity of RNF32 depends on calmodulin, the primary calcium sensor in eukaryotic cells. Increased levels of intracellular calcium ion (Ca2+) induce RNF32 binding to calmodulin, RNF32 activation, and autoubiquitylation. In turn, polyubiquitin chains conjugated to RNF32 recruit NEMO, the regulatory subunit of the IKK complex. Moreover, Ca2+ rise triggers RNF32 phase separation, which is required for the formation of NEMO condensates and IKK activation. Finally, we show that RNF32 is required for NF-κB activation triggered by bacterial lipopolysaccharides. Collectively, our findings uncover a mechanism controlling NF-κB signaling in the intestinal epithelium.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Y_244,

title = {In vitro and in vivo characterization of novel magnesium alloy implants enhanced by hydrothermal and sol-gel treatments for bone regeneration},

author = {Bellavia D and Paduano F and Brogini S and Ruggiero R and Marano RM and Cusanno A and Guglielmi P and Piccininni A and Pavarini M and D'Agostino A and Gambardella A and Peres C and Palumbo G and Chiesa R and Zappini G and Tatullo M and Giavaresi G},

url = {https://pubs.rsc.org/en/content/articlelanding/2025/tb/d5tb01282a},

doi = {10.1039/d5tb01282a},

year  = {2025},

date = {2025-11-19},

urldate = {2025-11-19},

journal = {Journal of materials chemistry B},

volume = {13},

issue = {43},

pages = {14032-14046},

abstract = {Magnesium alloys are emerging as promising materials for biodegradable orthopedic implants due to their mechanical strength and biocompatibility. However, their clinical use is hindered by rapid degradation and hydrogen gas evolution, which can compromise implant stability and bone healing. This study investigates the biocompatibility, genotoxicity, and osteointegration of magnesium implants (AZ31) produced via Superplastic Forming and enhanced through Hydrothermal and Sol-Gel surface treatments. Both techniques produced uniform Mg(OH)2-based coatings, but only alloy with hydrothermal treatment exhibited a markedly slower in vitro degradation. Cytotoxicity and Ames mutagenicity assays confirmed the biocompatibility and non-mutagenic nature of all implant types. In vivo evaluation in a rat femoral defect model revealed successful bone formation around all implant types, with comparable trabecular bone area. However, surface-treated implants showed a significantly lower bone-to-implant contact compared to the control AZ31 alloy, with solgel-treated alloys exhibiting an accelerated degradation rate and higher hydrogen release, which may influence tissue integration. These results highlight the role of surface modification in tuning degradation behavior and bone interface characteristics, with solgel-treated alloys resorbing faster. The combination of superplastic forming processing with strategic surface treatments offers a promising approach to achieving controlled biodegradation, although further optimization is needed to improve bone-implant integration. This work supports the further development of surface-engineered Mg implants for safe and functional orthopedic applications.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Y_243,

title = {Circular RNAs in Cardiovascular Physiopathology: From Molecular Mechanisms to Therapeutic Opportunities},

author = {Capirossi G and Brasini S and Tremoli E and Binatti A and Roncarati R},

url = {https://www.mdpi.com/1422-0067/26/19/9725},

doi = {10.3390/ijms26199725},

year  = {2025},

date = {2025-11-19},

journal = {International journal of molecular sciences},

volume = {26},

issue = {19},

pages = {9725},

abstract = {Circular RNAs are a class of stable non-coding RNAs generated through a back-splicing mechanism. They are now recognized as central players in cell function and are no longer considered byproducts of transcription. CircRNAs regulate gene expression at the transcriptional, post-transcriptional, and translational levels by interacting with various molecules. They act as sponges for miRNAs and proteins, molecular scaffolds, and can also be translated into peptides. Although advances in next-generation sequencing and PCR methods have improved their identification and quantification, technical and bioinformatic challenges remain. Increasing evidence shows their involvement in cardiovascular diseases such as heart failure, hypertrophy, fibrosis, and atherosclerosis, with protective or deleterious effects depending on the context. Given their presence in biological fluids and extracellular vesicles, they can be considered promising biomarkers, but their therapeutic applications are still under investigation. Future studies including a better understanding of their mechanisms of action, the development of standardized validation methods, and potential clinical applications (prevention, early diagnosis, personalized therapies) in diseases are still needed. This review provides an updated overview of the knowledge regarding circRNAs and their translational role in health and disease with a particular focus on cardiovascular diseases.},

note = {Review},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Y_242,

title = {Epidemiological and Clinical Data from the European lipodystrophy (ECLip) registry},

author = {Ceccarini G and Vatier C and Akinci B and Belalem I and Broekema M and Csajbok E and Rosaria D'Apice M and Gambineri A and Heldt K and Heni M and Kleinendorst L and Krause K and Lattanzi G and Miehle K and Palladino L and Prodam F and Santini F and Santos Silva E and Savage DB and Sbraccia P and Scherer T and Sorkina E and Stotl I and Vantyghem MC and Vigouroux C and Vorona E and Araujo-Vilar D and Wabitsch M and Nagel G and von Schnurbein J; ECLip Registry Consortium},

url = {https://academic.oup.com/ejendo/advance-article/doi/10.1093/ejendo/lvaf214/8305425?login=true},

doi = {10.1093/ejendo/lvaf214},

year  = {2025},

date = {2025-11-19},

journal = {European journal of endocrinology},

volume = {193},

issue = {5},

pages = {685-703},

abstract = {Objective: Lipodystrophy syndromes comprise a group of rare diseases characterized by loss of adipose tissue without nutritional or catabolic causes. As the rarity of these conditions necessitates collaboration, the European Consortium of Lipodystrophies (ECLip) established an international, longitudinal registry for patients with all forms of lipodystrophy (excluding HIV-associated cases). Methods: From December 2017 to November 2023, 19 centres from 13 countries recruited 631 patients into the ECLip registry. Cross-sectional data were analysed using descriptive statistics Results: Prospective data was available for 467 patients (82.7%, female; 86.5% adults; median age 44.0 years). Familial partial lipodystrophy (FPLD) was the most common subtype (57.4%), especially FPLD2 (37.9%). However, in men congenital generalized lipodystrophy was nearly as common as FPLD (33.3% vs. 35.8%). Symptoms at onset varied by subtype, with loss of adipose tissue being the most frequent. More than 70% of the patients suffered from metabolic complications, particularly dyslipidaemia (59.0%) and diabetes (48.4%) but prevalence and severity varied between subtypes (prevalence of diabetes for example 76.9% in patients with acquired partial lipodystrophy vs 8.7% in acquired localized lipodystrophy). Metreleptin, the only disease-specific treatment, was used by 11.6% of all patients. 34 deaths were documented, primarily due to cardiovascular events and cancer. Patients with generalized forms of lipodystrophy died earlier compared to patients with partial forms (median age at death 27.0 vs. 72.0 years). Conclusion: This study describes the largest cohort of patients with lipodystrophy reported to date. The dataset offers a comprehensive view of the epidemiology, clinical presentation, and associated comorbidities of lipodystrophy.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Y_241,

title = {Chromatin remodeling restrains oncogenic functions in prostate cancer},

author = {Rosti V and Lembo G and Petrini C and Gorini F and Quadri R and Cordiglieri C and Mutarelli M and Salviato E and Casari E and Di Patrizio Soldateschi E and Montanari E and Albo G and Ripa F and Fasciani A and Crosti M and De Lorenzis E and Maggioni M and Vaira V and Vivo M and Ferrari F and Lanzuolo C},

url = {https://www.nature.com/articles/s41467-025-64213-4},

doi = {10.1038/s41467-025-64213-4},

year  = {2025},

date = {2025-10-21},

journal = {Nature Communications},

volume = {16},

pages = {9174},

abstract = {Primary prostate cancer presents with multifocal lesions and unpredictable clinical behavior, posing significant challenges for effective prognosis. To address this, we investigate the epigenomic landscape of prostate tumor biopsies from 25 treatment-naïve male patients by analyzing chromatin compartmentalization patterns. Our analysis reveals two distinct molecular subtypes: one with a Low Degree of Decompartmentalization (LDD) and another with a High Degree of Decompartmentalization (HDD). Here we show that the HDD subgroup exhibits extensive chromatin reorganization associated with diminished oncogenic potential. This subtype shows repression of molecular pathways involved in extracellular matrix remodeling and cellular plasticity. From this distinction, we derive an 18-gene transcriptional signature capable of differentiating HDD from LDD cases. Importantly, we validate the prognostic relevance of this signature in multiple independent cohorts totaling over 900 patients. Our findings suggest that epigenetic-derived signature at the time of diagnostic biopsy can offer a powerful tool for risk stratification in prostate cancer.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Y_240,

title = {Spiroplasma impairs testes gene expression in Glossina fuscipes fuscipes},

author = {Piccinno R and Fiorenza G and Lescai F and Carpanzano S and Gstottenmayer F and Dera KM and Croce AC and de Beer CJ and Santorsola M and Gasperi G and Forneris F and Abd-Alla AMM and Aksoy S and Malacrida AR},

url = {https://www.biorxiv.org/content/10.1101/2025.09.23.678099v1},

doi = {10.1101/2025.09.23.678099},

year  = {2025},

date = {2025-10-21},

urldate = {2025-10-21},

journal = {bioRxiv (PREPRINT)},

volume = {2025.09.23.678099},

abstract = {Glossina fuscipes fuscipes is a riverine tsetse fly species, the primary vector of human and animal trypanosomiasis in Sub-Saharan Africa. Controlling tsetse fly populations is crucial for mitigating the socio-economic impact of this disease, as effective treatments remain challenging. Indeed, the development of control strategies is hindered by the species' unique reproductive biology: adenotrophic viviparity, in which the female retains and nourishes the developing larva in her uterus throughout the pregnancy. The discovery of Spiroplasma in some G. f. fuscipes populations has drawn attention as a potential tool to enhance tsetse fly control strategies. Although Spiroplasma does not exhibit in G. f. fuscipes the male-killing phenotype observed in Drosophila melanogaster, evidence suggests that it may confer refractoriness to Trypanosoma infection. This has led to further investigations into its broader effects on G. f. fuscipes biology, particularly its potential impact on Glossina reproductive fitness. In this study, we considered Spiroplasma effect on the male reproduction. For this, we performed a differential gene expression analysis on testes and male accessory glands (MAGs) between Spiroplasma-infected and uninfected males. A significant downregulation of genes was observed in testes while a minor effect has been detected on MAGs. Downregulation of testes genes associated with functions related to sperm motility, energy metabolism, and mitochondrial function has been observed. Additionally, differentially expressed genes involved in antimicrobial activity and circadian rhythm regulation were observed. These findings provide valuable insights into the potential fitness costs of Spiroplasma infection for the fly and its implications for the bacterium use as biological control strategies targeting G. f. fuscipes.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Y_239,

title = {Spontaneous activity of astrocytes is a stochastic functional signal for memory consolidation},

author = {Losi G and Vignoli B and Granata R and Lia A and Zonta M and Sansevero G and Pischedda F and Chiavegato A and Santi S and Zentilin L and Berardi N and Ratto GM and Carmignoto G and Canossa M},

url = {https://www.pnas.org/doi/10.1073/pnas.2500511122?url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org&rfr_dat=cr_pub++0pubmed},

doi = {10.1073/pnas.2500511122},

year  = {2025},

date = {2025-10-21},

journal = {Proceedings of the National Academy of Sciences of the United States of America},

volume = {122},

issue = {42},

pages = {e2500511122},

abstract = {In the absence of explicit neuronal inputs, the glial cell astrocytes exhibit recurring intracellular Ca2+ fluctuations, primarily localized at thin processes, known as Ca2+ microdomains (MDs). Although spontaneous Ca2+ MDs are present throughout the brain, their putative role is unknown. Here, we question whether, owing to their recurring signaling mode, spontaneous Ca2+ MDs contribute to slowly evolving phenomena in the brain, such as memory consolidation. We demonstrate that, in the perirhinal cortex, a central region in recognition memory, these events promote Ca2+-dependent gliotransmission and modulate synaptic strengthening. Their recurring activity extends the release of the gliotransmitter brain-derived neurotrophic factor (BDNF) over time, ensuring the sustained Tropomyosin Receptor Kinase B (TrkB)-signaling required for the consolidation of long-term synaptic potentiation and lasting memories. We also show that Ca2+ MDs, which are stochastic events, preserve their random behavior during gliotransmission, introducing an element of unpredictability into the process of memory retention. Our study assigns to spontaneous, stochastic activity in astrocytes a unique functional role in shaping and stabilizing memory circuits.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Y_222,

title = {ANKRD2 Knockdown as a Therapeutic Strategy in Osteosarcoma: Effects on Proliferation and Drug Response in U2OS and HOS Cells},

author = {Cenni V and Bavelloni A and Capanni C and Mattioli E and Bortolozzo F and Kojic S and Orlandi G and Bertacchini J and Blalock WL},

url = {https://www.mdpi.com/1422-0067/26/4/1736},

doi = {10.3390/ijms26041736},

year  = {2025},

date = {2025-10-21},

urldate = {2025-08-11},

journal = {International journal of molecular sciences},

volume = {26},

issue = {4},

pages = {1736},

abstract = {Ankrd2, a mechanoresponsive protein primarily studied in muscle physiology, is emerging as a player in cancer progression. This study investigates the functional role of Ankrd2 in osteosarcoma cells, revealing its critical involvement in cell proliferation and response to chemotherapeutic drugs. We showed that Ankrd2 knockdown impairs the activation of PI3K/Akt and ERK1/2 pathways, reduces levels of cell cycle regulators including cyclin D1 and cyclin B, and counteracts the expression of nuclear lamin A and lamin B, disrupting nuclear morphology and DNA integrity. Strikingly, the loss of Ankrd2 enhances the sensitivity of osteosarcoma cells to doxorubicin and cisplatin, highlighting Ankrd2 potential as a therapeutic target to improve chemotherapeutic efficacy. Defining a novel mechanistic role for Ankrd2 in promoting tumor progression, we propose that Ankrd2 reduction could be exploited as an adjuvant strategy to enhance the efficacy of chemotherapy, offering new therapeutic opportunities for OS treatment.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Y_218,

title = {In vitro study of cold atmospheric plasma-induced proliferation inhibition and morphological changes in head and neck carcinoma cell lines},

author = {Maravic T and Petrucci G and Giacomo VD and Mazzitelli C and Acharya TR and Kaushik NK and Choi EH and Rapino M and D'Urso D and Josic U and Caponio VCA and Micaroni M and Edoardo M and Russo LL and Muzio LL and Breschi L and Perotti V},

url = {https://www.sciencedirect.com/science/article/pii/S0300571225004518?via%3Dihub},

doi = {10.1016/j.jdent.2025.106007},

year  = {2025},

date = {2025-10-21},

urldate = {2025-08-11},

journal = {Journal of dentistry},

volume = {161},

pages = {106007},

abstract = {"Objectives: The use of cold atmospheric plasma (CAP) has been growing in medical field. Since limited data exist on the influence of CAP exposure on head and neck cancer (HNC) cells, we aimed to investigate in vitro its impact on proliferation and morphology of HNC (HSC2, HSC3, and FaDu) cells, as well as healthy gingival fibroblasts (hGF).

Methods: A CAP gas air jet was applied directly on the HSC2, HSC3, FaDu and hGF cells for 30 and 60 s; doxorubicin has been used as positive control. Inhibition of cell proliferation at different time points (24, 48, and 72 h) was investigated through MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium]. Morphological alterations were observed using scanning electron microscope (SEM) and transmission electron microscope (TEM). Data were statistically analyzed (p < 0.05). Results: CAP exposure of 60 s showed the highest proliferation inhibitory effects in all investigated cancer cell lines (p < 0.001). While HSC2 had the highest proliferation inhibition at 24 h, HSC3, and FaDu exhibited a positive, time-dependent inhibitory effect (24 < 48 < 72 h) after CAP exposure. Interestingly, effects of CAP in the hGF were minimal. SEM observations revealed morphological changes in HNC cells treated with CAP at 30 and 60 s. Moreover, TEM showed stressed conditions in the survived HNC cells at 48 h after CAP exposure demonstrated by the presence of multilamellar and multi-vesicular bodies. Conclusions: CAP treatment induced proliferation inhibition, morphologic changes and stressed conditions in HNC cell lines (HSC2, HSC3, and FaDu), while demonstrating limited effects on hGF cells.Clinical significance: This work characterized early cellular responses of HSC2, HSC3, and FaDu to CAP exposure, including proliferation, and morphology, as foundational data before progressing to more clinically representative models."},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Y_215,

title = {Sammy Basso, his life and message, and the importance of progeria research},

author = {Lattanzi G},

url = {https://academic.oup.com/eurheartj/advance-article/doi/10.1093/eurheartj/ehaf355/8160766?login=true#google_vignette},

doi = {10.1093/eurheartj/ehaf355},

year  = {2025},

date = {2025-10-21},

urldate = {2025-08-11},

journal = {European heart journal},

volume = {46},

number = {2945-2946},

issue = {30},

abstract = {not available},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = {Trichothiodystrophy: Molecular insights and mechanisms of pathogenicity},

author = {Lanzafame M and Brevi F and Veniali G and Botta E},

url = {https://www.sciencedirect.com/science/article/pii/S1383574225000262?via%3Dihub},

doi = {10.1016/j.mrrev.2025.108555},

year  = {2025},

date = {2025-10-21},

urldate = {2025-08-11},

journal = {Mutation research. Reviews in mutation research},

volume = {796},

pages = {108555},

abstract = {Trichothiodystrophy (TTD) is a rare hereditary disease characterized by brittle, sulphur deficient hair associated with a wide and varied spectrum of clinical features which include skin alterations, neurodevelopmental defects, and immune dysfunction. The presence of hypersensitivity to UV light defines the two main forms of TTD: photosensitive (PS-TTD) and non-photosensitive (NPS-TTD). The disease arises from mutations in a variety of genes involved in different biological processes. Affected processes include DNA repair, transcription as well as translation. This review provides the latest vision of TTD: from up-to-date mutational spectra and genotype-phenotype relationships to our current understanding of the pathogenic mechanisms that underlie the complex etiology of this multi-faceted disease.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Y_237,

title = {Proceedings of the annual meeting of the European Consortium of Lipodystrophies (ECLip) Paris, France, 20-21 May 2025},

author = {Vatier C and Araujo-Vilar D and Akinci B and Arnould T and Beaupère C and Bismuth E and Brown RJ and Ceccarini G and Collas P and Gambineri A and Gilio D and Halperin S and Janmaat S and Lamothe S and Lattanzi G and Maffei M and MacDougald OA and Mosbah H and Nobecourt E and Oral EA and Rochford J and Santini F and Schirmer EC and von Schnurbein J and Semple R and Tews D and Wabitsch M and Vantyghem MC and Vigouroux C},

url = {https://www.sciencedirect.com/science/article/pii/S0003426625007516?via%3Dihub},

doi = {10.1016/j.ando.2025.102432},

year  = {2025},

date = {2025-10-10},

journal = {Annales de endocrinologie},

volume = {86},

issue = {5},

pages = {102432},

abstract = {Lipodystrophy syndromes are rare diseases characterized by anatomical and functional defects of adipose tissue, frequently leading to severe insulin resistance-associated metabolic complications. Subtypes of lipodystrophy syndromes differ in: their clinical presentation, with generalized or partial loss of adipose tissue; in their origin, either genetic or acquired; and in their comorbidities, forming a heterogeneous group of disorders of different severity. The European Consortium of Lipodystrophies (ECLip) was founded in 2014 as a non-profit network of health professionals, scientists and patient associations. ECLip aims to promote international collaborations to increase pathophysiological and clinical knowledge, and improve the management of lipodystrophy syndromes. ECLip now comprises 59 groups from 30 countries from Europe and beyond. The consortium developed in parallel to the increased awareness of clinical diagnosis, the growing scientific interest for these diseases at the crossroads between adipose tissue biology, whole body metabolism, genetics and immunity, and to the emergence of new pharmacological approaches. The ECLip congress, held every 18 months, aims to discuss the recent achievements and projects in the field of lipodystrophies, to consolidate ECLip activities and to promote future collaborations, highlighting clinical and fundamental aspects as well as patients' perspectives. Oral communications presented during the meeting in Paris, France, in 2025 are summarized in these minutes.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Y_212,

title = {Fatty acid binding protein 1 (FABP1) depletion promotes an oxidative metabolic shift in Caco-2 colorectal cancer cells},

author = {Borus DL and Zadra G and Minsky D and Costa ML and Corsico B and Storch J and Scaglia N},

url = {https://www.sciencedirect.com/science/article/pii/S1388198125000691?via%3Dihub},

doi = {10.1016/j.bbalip.2025.159661},

year  = {2025},

date = {2025-10-06},

urldate = {2025-08-11},

journal = {Biochimica et biophysica acta. Molecular and cell biology of lipids},

volume = {1870},

issue = {7},

pages = {159661},

abstract = {Lipid metabolism reprogramming is a well-established hallmark of many cancer types, including colorectal cancer (CRC). Nevertheless, a clear understanding on how fatty acid (FA) metabolism is fine-tuned during CRC development and progression is still missing. Given that CRC is the second leading cause of cancer-related death, addressing these critical aspects may provide the rationale for new therapeutic approaches and early biomarker identification. Fatty acid binding protein 1 (FABP1) is a small protein that binds FA and other lipophilic compounds, acting as a lipid transporter in the intestine. Little is currently known about the function of FABP1 in CRC. Here we show that the knockdown of FABP1 in CRC cells impairs de novo FA and cholesterol synthesis, specifically, via altering the transcriptional regulation of lipid metabolism genes. FABP1 depletion suppresses the expression of FA and cholesterol synthesis-associated genes while promoting that of FA oxidation genes and mitochondrial oxidative pathways. The latter is associated with increased oxygen consumption rate and activation of the energy sensor 5' AMP-activated kinase (AMPK). Taken together, our results show that FABP1 orchestrates the balance between FA synthesis and oxidation, most likely to prevent the cytotoxic effects of circulating unbound free fatty acids. Thus, targeting FABP1 function may represent a potential therapeutic strategy in advanced CRC.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Y_236,

title = {Proceedings of the annual meeting of the European Consortium of Lipodystrophies (ECLip) Paris, France, 20-21 May 2025},

author = {Vatier C and Araujo-Vilar D and Akinci B and Arnould T and Beaupere C and Bismuth E and Brown RJ and Ceccarini G and Collas P and Gambineri A and Gilio D and Halperin S and Janmaat S and Lamothe S and Lattanzi G and Maffei M and MacDougald OA and Mosbah H and Nobecourt E and Oral EA and Rochford J and Santini F and Schirmer EC and von Schnurbein J and Semple R and Tews D and Wabitsch M and Vantyghem MC and Vigouroux C},

url = {https://www.sciencedirect.com/science/article/pii/S0003426625007516?via%3Dihub},

doi = {10.1016/j.ando.2025.102432},

year  = {2025},

date = {2025-09-29},

journal = {Annales de endocrinologie},

volume = {86},

issue = {5},

pages = {102432},

abstract = {Lipodystrophy syndromes are rare diseases characterized by anatomical and functional defects of adipose tissue, frequently leading to severe insulin resistance-associated metabolic complications. Subtypes of lipodystrophy syndromes differ in: their clinical presentation, with generalized or partial loss of adipose tissue; in their origin, either genetic or acquired; and in their comorbidities, forming a heterogeneous group of disorders of different severity. The European Consortium of Lipodystrophies (ECLip) was founded in 2014 as a non-profit network of health professionals, scientists and patient associations. ECLip aims to promote international collaborations to increase pathophysiological and clinical knowledge, and improve the management of lipodystrophy syndromes. ECLip now comprises 59 groups from 30 countries from Europe and beyond. The consortium developed in parallel to the increased awareness of clinical diagnosis, the growing scientific interest for these diseases at the crossroads between adipose tissue biology, whole body metabolism, genetics and immunity, and to the emergence of new pharmacological approaches. The ECLip congress, held every 18 months, aims to discuss the recent achievements and projects in the field of lipodystrophies, to consolidate ECLip activities and to promote future collaborations, highlighting clinical and fundamental aspects as well as patients' perspectives. Oral communications presented during the meeting in Paris, France, in 2025 are summarized in these minutes.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Y_233,

title = {Tracking micro- and nanoplastics in Aedes albopictus: From ingestion to metabolic disruption},

author = {Soldano S and Bonanomi M and Aramini T and Moyano A and Garbelli A and Croce AC and Weththimuni ML and Vaghi P and Puggioli A and Gomulski LM and Gaglio D and Scolari F},

url = {https://www.sciencedirect.com/science/article/pii/S004896972502087X?via%3Dihub},

doi = {10.1016/j.scitotenv.2025.180447},

year  = {2025},

date = {2025-09-29},

urldate = {2025-09-29},

journal = {The Science of the total environment},

volume = {1002},

pages = {180447},

abstract = {Urban aquatic environments are increasingly contaminated with micro- and nanoplastics (MNLPs), posing risks to biodiversity and human health. These environments are ideal breeding sites for larvae of the Asian tiger mosquito Aedes albopictus, a key arbovirus vector. While plastic pollution is a global concern, physiological and metabolic consequences of MNPL-exposure in mosquitoes remain poorly understood. Combining epifluorescence and confocal imaging, mosquito life-history parameter assessment, and high-throughput metabolomic profiling, we investigated the effects of polystyrene MNPLs on Ae. albopictus. We demonstrated that ingested MNPLs cross the larval gut barrier, persist in various tissues, and are retained through development. Exposure did not significantly affect pre-imaginal survival or development time, but reduced larval body weight and caused profound metabolic alterations. Metabolomic analyses revealed downregulation of central carbon metabolism, particularly glycolysis and pentose phosphate pathway, alongside amino acid alterations linked to stress responses. Notably, MNPL-exposure also affected juvenile hormone biosynthesis, suggesting endocrine disruption. This trend was observed in both NP- and MP-exposed larvae, with a greater number of differentially regulated metabolites following MP-treatment. Interestingly, TCA cycle dysregulation was more pronounced in NP-exposed larvae, whereas perturbations in glutathione metabolism, amino sugar metabolism and nitrogen excretion were associated with MP-exposure. These findings highlight the metabolic and physiological consequences of MNPL-exposure, with potential implications for mosquito ecology, vector capacity, and environmental dissemination of plastic contaminants. Given the role of Ae. albopictus in disease transmission and its adaptation to urban habitats, further research is needed to explore the long-term ecological and epidemiological consequences of plastic pollution on mosquito populations.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Y_232,

title = {Telomeric DNA damage response mediates neurotoxicity of Aβ42 oligomers in Alzheimer's disease},

author = {Sepe S and Rey F and Mancheno-Ferris A and Bigi A and Fani G and Damiani D and Cabrini M and Marinelli E and Aguado J and Contu L and di Lillo A and Boggio S and Tavella S and Rosso I and Gustincich S and Chiti F and {d'Adda di Fagagna F},

doi = {10.1038/s44318-025-00521-1},

year  = {2025},

date = {2025-09-29},

urldate = {2025-09-29},

journal = {EMBO Journal},

volume = {44},

issue = {21},

pages = {6078-6111},

abstract = {Ageing is the major risk factor for Alzheimer's disease (AD), the most common neurodegenerative disorder. DNA damage is a hallmark of ageing, particularly when occurring at telomeres, genomic regions vulnerable to oxidative damage and often challenging for the cell to repair. Here, we show that brains of 3xTg-AD mice, an established AD model characterized by amyloid-β (Aβ)-induced pathology, exhibit increased activation of DNA damage response (DDR) pathways at telomeres. Exposure of mouse primary hippocampal neurons to 42-residue Aβ (Aβ42) oligomers, a significant pathogenetic contributor to AD, triggers telomeric DDR by increasing the levels of reactive oxygen species caused by calcium imbalance. Antisense oligonucleotides targeting non-coding RNAs generated at damaged telomeres in vivo (in 3xTg-AD mice) and in vitro reduce neurotoxicity in iPSC-derived human cortical neurons and mouse primary neurons while inhibiting Aβ42-induced telomeric DDR, and restore transcriptional pathways altered by Aβ and found dysregulated in AD patients. These results unveil an unexpected role of telomeric DNA damage responses in Alzheimer's disease pathogenesis, and suggest a novel target for the development of RNA-based therapies.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Y_231,

title = {SOD-1/2 Involvement in the Antioxidant Molecular Events Occurring upon Complex Magnetic Fields Application in an In Vitro H2O2 Oxidative Stress-Induced Endothelial Cell Model},

author = {Ricci A and Zara S and di Giacomo V and Gallorini M and Rapino M and Di Pietro N and Cipollina A and Piattelli A and Cataldi A},

url = {https://www.mdpi.com/1422-0067/26/17/8600},

doi = {10.3390/ijms26178600},

year  = {2025},

date = {2025-09-29},

journal = {International journal of molecular sciences},

volume = {26},

issue = {17},

pages = {8600},

abstract = {"Endothelial function plays a key role in tissue repair. Reactive Oxygen Species (ROS) production impairs tissue renewal and homeostasis. Complex Magnetic Fields (CMFs) have been attracting attention as a non-invasive tool to promote tissue regeneration, especially through angiogenic stimulation. The present study aims to investigate CMF effect in an in vitro model of oxidative stress-stimulated Endothelial Cells (ECs). Cells were pre-treated with H2O2 to mimic an oxidative environment, followed by the application of three CMF programs repeated in two experimental sets: two consecutive cycles (two cycles) or two cycles spaced 24 h apart (T0+T24). Flow cytometry investigation shows that both CMF applications reduce ROS production, presumably promoting SODs proteins expression. Specifically, two cycles affect mitochondrial SOD-2 expression, which may promote cellular turnover by upregulating pro-apoptotic proteins, leading to mild cell death balanced with increased cell viability. T0+T24 application promotes cytosolic SOD-1 expression, which may influence the expression and release of antioxidant molecules, as evidenced by the increased protein levels of Akt/Nrf2 and the overall antioxidant activity measured post-treatment. In conclusion, ROS-induced EC dysfunction can be reverted by CMF application: 2 cycles could be applied when cellular renewal is required (such as in pathological wounds) while T0+T24 could be useful when an antioxidant and anti-inflammatory effect is needed (e.g., in edema or muscular lesions).},

keywords = {},

pubstate = {published},

tppubtype = {article}

}