@article{%a1.%Y_125,

title = {Proteomic Analysis on Sequential Samples of Cystic Fluid Obtained from Human Brain Tumors},

author = {Magrassi L and Brambilla F and Viganò R and Di Silvestre D and Benazzi L and Bellantoni G and Danesino GM and Comincini S and Mauri P},

url = {https://www.mdpi.com/2072-6694/15/16/4070},

doi = {10.3390/cancers15164070},

year  = {2023},

date = {2023-12-07},

journal = {Cancers-Basel},

volume = {15},

issue = {16},

pages = {4070},

abstract = {Cystic formation in human primary brain tumors is a relatively rare event whose incidence varies widely according to the histotype of the tumor. Composition of the cystic fluid has mostly been characterized in samples collected at the time of tumor resection and no indications of the evolution of cystic content are available. We characterized the evolution of the proteome of cystic fluid using a bottom-up proteomic approach on sequential samples obtained from secretory meningioma (SM), cystic schwannoma (CS) and cystic high-grade glioma (CG). We identified 1008 different proteins; 74 of these proteins were found at least once in the cystic fluid of all tumors. The most abundant proteins common to all tumors studied derived from plasma, with the exception of prostaglandin D2 synthase, which is a marker of cerebrospinal fluid origin. Overall, the protein composition of cystic fluid obtained at different times from the same tumor remained stable. After the identification of differentially expressed proteins (DEPs) and the protein-protein interaction network analysis, we identified the presence of tumor-specific pathways that may help to characterize tumor-host interactions. Our results suggest that plasma proteins leaking from local blood-brain barrier disruption are important contributors to cyst fluid formation, but cerebrospinal fluid (CSF) and the tumor itself also contribute to the cystic fluid proteome and, in some cases, as with immunoglobulin G, shows tumor-specific variations that cannot be simply explained by differences in vessel permeability or blood contamination.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Y_124,

title = {Impact of heat and cold shock on epigenetics and chromatin structure},

author = {Casali C and Galgano L and Zannino L and Siciliani S and Cavallo M and Mazzini G and Biggiogera M},

url = {https://www.sciencedirect.com/science/article/pii/S0171933523000882?via%3Dihub},

doi = {10.1016/j.ejcb.2023.151373},

year  = {2023},

date = {2023-12-02},

urldate = {2024-01-28},

journal = {European journal of cell biology},

volume = {103},

issue = {1},

pages = {151373},

abstract = {Cells are continuously exposed to various sources of insults, among which temperature variations are extremely common. Epigenetic mechanisms, critical players in gene expression regulation, undergo alterations due to these stressors, potentially leading to health issues. Despite the significance of DNA methylation and histone modifications in gene expression regulation, their changes following heat and cold shock in human cells remain poorly understood. In this study, we investigated the epigenetic profiles of human cells subjected to hyperthermia and hypothermia, revealing significant variations. Heat shock primarily led to DNA methylation increments and epigenetic modifications associated with gene expression silencing. In contrast, cold shock presented a complex scenario, with both methylation and demethylation levels increasing, indicating different epigenetic responses to the opposite thermal stresses. These temperature-induced alterations in the epigenome, particularly their impact on chromatin structural organization, represent an understudied area that could offer important insights into genome function and potential prospects for therapeutic targets.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Y_128,

title = {A modular phage vector platform for targeted photodynamic therapy of Gram-negative bacterial pathogens},

author = {Petrosino A and Saporetti R and Starinieri F and Sarti E and Ulfo L and Boselli L and Cantelli A and Morini A and Zadran SK and Zuccheri G and Pasquini Z and Di Giosia M and Prodi L and Pompa PP and Costantini PE and Calvaresi M and Danielli A},

url = {https://www.sciencedirect.com/science/article/pii/S2589004223021090?via%3Dihub},

doi = {10.1016/j.isci.2023.108032},

year  = {2023},

date = {2023-10-18},

journal = {ISCIENCE},

volume = {26},

issue = {10},

pages = {108032},

abstract = {Growing antibiotic resistance has encouraged the revival of phage-inspired antimicrobial approaches. On the other hand, photodynamic therapy (PDT) is considered a very promising research domain for the protection against infectious diseases. Yet, very few efforts have been made to combine the advantages of both approaches in a modular, retargetable platform. Here, we foster the M13 bacteriophage as a multifunctional scaffold, enabling the selective photodynamic killing of bacteria. We took advantage of the well-defined molecular biology of M13 to functionalize its capsid with hundreds of photo-activable Rose Bengal sensitizers and contemporarily target this light-triggerable nanobot to specific bacterial species by phage display of peptide targeting moieties fused to the minor coat protein pIII of the phage. Upon light irradiation of the specimen, the targeted killing of diverse Gram(-) pathogens occurred at subnanomolar concentrations of the phage vector. Our findings contribute to the development of antimicrobials based on targeted and triggerable phage-based nanobiotherapeutics.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Y_132,

title = {Mineralocorticoid Receptor Antagonism Prevents Type 2 Familial Partial Lipodystrophy Brown Adipocyte Dysfunction},

author = {Schena E and Mattioli E and Peres C and Zanotti L and Morselli P and Iozzo P and Guzzardi MA and Bernardini C and Forni M and Nesci S and Caprio M and Cecchetti C and Pagotto U and Gabusi E and Cattini L and Lisignoli G and Blalock WL and Gambineri A and Lattanzi G},

url = {https://www.mdpi.com/2073-4409/12/22/2586},

doi = {10.3390/cells12222586},

year  = {2023},

date = {2023-10-10},

urldate = {2023-10-10},

journal = {CELLS},

volume = {12},

issue = {22},

pages = {2586},

abstract = {Type-2 Familial Partial Lipodystrophy (FPLD2), a rare lipodystrophy caused by LMNA mutations, is characterized by a loss of subcutaneous fat from the trunk and limbs and excess accumulation of adipose tissue in the neck and face. Several studies have reported that the mineralocorticoid receptor (MR) plays an essential role in adipose tissue differentiation and functionality. We previously showed that brown preadipocytes isolated from a FPLD2 patient's neck aberrantly differentiate towards the white lineage. As this condition may be related to MR activation, we suspected altered MR dynamics in FPLD2. Despite cytoplasmic MR localization in control brown adipocytes, retention of MR was observed in FPLD2 brown adipocyte nuclei. Moreover, overexpression of wild-type or mutated prelamin A caused GFP-MR recruitment to the nuclear envelope in HEK293 cells, while drug-induced prelamin A co-localized with endogenous MR in human preadipocytes. Based on in silico analysis and in situ protein ligation assays, we could suggest an interaction between prelamin A and MR, which appears to be inhibited by mineralocorticoid receptor antagonism. Importantly, the MR antagonist spironolactone redirected FPLD2 preadipocyte differentiation towards the brown lineage, avoiding the formation of enlarged and dysmorphic lipid droplets. Finally, beneficial effects on brown adipose tissue activity were observed in an FPLD2 patient undergoing spironolactone treatment. These findings identify MR as a new lamin A interactor and a new player in lamin A-linked lipodystrophies.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Yb_122,

title = {Hot on RAD51C: structure and functions of RAD51C-XRCC3},

author = {Szakal B and Branzei D},

url = {https://febs.onlinelibrary.wiley.com/doi/10.1002/1878-0261.13518},

doi = {10.1002/1878-0261.13518},

year  = {2023},

date = {2023-10-05},

urldate = {2023-10-05},

journal = {Molecular oncology},

volume = {17},

issue = {10},

pages = {1950-1952},

abstract = {A new study by Longo, Roy et al. has solved the structure of the RAD51C-XRCC3 (CX3) heterodimer with a bound ATP analog, identifying two main structural interfaces and defining separable replication fork stability roles. One function relates to the ability of RAD51C to bind and assemble CX3 on nascent DNA, with an impact on the ability of forks to restart upon replication stress. The other relates to effective CX3 heterodimer formation, required for 5' RAD51 filament capping, with effects on RAD51 filament disassembly, fork protection and influencing the persistence of reversed forks.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Yb_121,

title = {PCNA recruits cohesin loader Scc2 to ensure sister chromatid cohesion},

author = {Psakhye I and Kawasumi R and Abe T and Hirota K and Branzei D},

url = {https://www.nature.com/articles/s41594-023-01064-x},

doi = {10.1038/s41594-023-01064-x.},

year  = {2023},

date = {2023-10-05},

journal = {Nature structural & molecular biology},

volume = {30},

issue = {9},

pages = {1286-1294},

abstract = {Sister chromatid cohesion, established during replication by the ring-shaped multiprotein complex cohesin, is essential for faithful chromosome segregation. Replisome-associated proteins are required to generate cohesion by two independent pathways. One mediates conversion of cohesins bound to unreplicated DNA ahead of replication forks into cohesive entities behind them, while the second promotes cohesin de novo loading onto newly replicated DNA. The latter process depends on the cohesin loader Scc2 (NIPBL in vertebrates) and the alternative PCNA loader CTF18-RFC. However, the mechanism of de novo cohesin loading during replication is unknown. Here we show that PCNA physically recruits the yeast cohesin loader Scc2 via its C-terminal PCNA-interacting protein motif. Binding to PCNA is crucial, as the scc2-pip mutant deficient in Scc2-PCNA interaction is defective in cohesion when combined with replisome mutants of the cohesin conversion pathway. Importantly, the role of NIPBL recruitment to PCNA for cohesion generation is conserved in vertebrate cells.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Yb_120,

title = {New Clinical and Immunofluoresence Data of Collagen VI-Related Myopathy: A Single Center Cohort of 69 Patients},

author = {Merlini L and Sabatelli P and Gualandi F and Redivo E and Di Martino A and Faldini C},

url = {https://www.mdpi.com/1422-0067/24/15/12474},

doi = {10.3390/ijms241512474},

year  = {2023},

date = {2023-10-05},

journal = {International journal of molecular sciences},

volume = {24},

issue = {15},

pages = {12474},

abstract = {Pathogenetic mechanism recognition and proof-of-concept clinical trials were performed in our patients affected by collagen VI-related myopathies. This study, which included 69 patients, aimed to identify innovative clinical data to better design future trials. Among the patients, 33 had Bethlem myopathy (BM), 24 had Ullrich congenital muscular dystrophy (UCMD), 7 had an intermediate phenotype (INTM), and five had myosclerosis myopathy (MM). We obtained data on muscle strength, the degree of contracture, immunofluorescence, and genetics. In our BM group, only one third had a knee extension strength greater than 50% of the predicted value, while only one in ten showed similar retention of elbow flexion. These findings should be considered when recruiting BM patients for future trials. All the MM patients had axial and limb contractures that limited both the flexion and extension ranges of motion, and a limitation in mouth opening. The immunofluorescence analysis of collagen VI in 55 biopsies from 37 patients confirmed the correlation between collagen VI defects and the severity of the clinical phenotype. However, biopsies from the same patient or from patients with the same mutation taken at different times showed a progressive increase in protein expression with age. The new finding of the time-dependent modulation of collagen VI expression should be considered in genetic correction trials.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Yb_119,

title = {N-Sulfenylation of beta-Lactams: Radical Reaction of N-Bromo-azetidinones by TEMPO Catalysis},

author = {Giraldi V and Giunchino F and Casacchia ME and Cantelli A and Lucarini M and Giacomini D},

url = {https://pubs.acs.org/doi/10.1021/acs.joc.3c01759},

doi = {10.1021/acs.joc.3c01759},

year  = {2023},

date = {2023-10-05},

urldate = {2023-10-05},

journal = {Journal of organic chemistry},

volume = {88},

number = {14728},

issue = {20},

pages = {14735},

abstract = {Azetidinones with a sulfenyl group on the β-lactam nitrogen atom show interesting biological activities as antimicrobial agents and enzyme inhibitors. We report in the present study a versatile synthesis of N-sulfenylated azetidinones starting from the corresponding N-bromo derivatives by means of the (2,2,6,6-tetramethylpiperidin-1-yl)oxyl (TEMPO) radical as the catalyst and disulfides. Preparation of N-halo-azetidinones was studied and optimized. The reactivity of N-bromo-azetidinone 2a as a model compound in the presence of TEMPO radical was investigated by NMR and electron paramagnetic resonance (EPR) spectroscopy studies. Optimization of the reaction conditions allowed the access of N-alkylthio- or N-arylthio-azetidinones from 55 to 92% yields, and the method exhibited a good substrate scope.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Yb_117,

title = {Epigenomic signature of accelerated ageing in progeroid Cockayne syndrome},

author = {Crochemore C and Chica C and Garagnani P and Lattanzi G and Horvath S and Sarasin A and Franceschi C and Bacalini MG and Ricchetti M},

url = {https://onlinelibrary.wiley.com/doi/10.1111/acel.13959},

doi = {10.1111/acel.13959},

year  = {2023},

date = {2023-10-05},

urldate = {2023-10-05},

journal = {Aging Cell},

volume = {22},

issue = {10},

pages = {e13959},

abstract = {Cockayne syndrome (CS) and UV-sensitive syndrome (UVSS) are rare genetic disorders caused by mutation of the DNA repair and multifunctional CSA or CSB protein, but only CS patients display a progeroid and neurodegenerative phenotype, providing a unique conceptual and experimental paradigm. As DNA methylation (DNAm) remodelling is a major ageing marker, we performed genome-wide analysis of DNAm of fibroblasts from healthy, UVSS and CS individuals. Differential analysis highlighted a CS-specific epigenomic signature (progeroid-related; not present in UVSS) enriched in three categories: developmental transcription factors, ion/neurotransmitter membrane transporters and synaptic neuro-developmental genes. A large fraction of CS-specific DNAm changes were associated with expression changes in CS samples, including in previously reported post-mortem cerebella. The progeroid phenotype of CS was further supported by epigenomic hallmarks of ageing: the prediction of DNAm of repetitive elements suggested an hypomethylation of Alu sequences in CS, and the epigenetic clock returned a marked increase in CS biological age respect to healthy and UVSS cells. The epigenomic remodelling of accelerated ageing in CS displayed both commonalities and differences with other progeroid diseases and regular ageing. CS shared DNAm changes with normal ageing more than other progeroid diseases do, and included genes functionally validated for regular ageing. Collectively, our results support the existence of an epigenomic basis of accelerated ageing in CS and unveil new genes and pathways that are potentially associated with the progeroid/degenerative phenotype.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Yb_118,

title = {Woven bone formation and mineralization by rat mesenchymal stromal cells imply increased expression of the intermediate filament desmin},

author = {{Di Conza G} and Barbaro F and Zini N and Spaletta G and Remaggi G and Elviri L and Mosca S and Caravelli S and Mosca M and Toni R.},

url = {https://www.frontiersin.org/articles/10.3389/fendo.2023.1234569/full},

doi = {10.3389/fendo.2023.1234569},

year  = {2023},

date = {2023-10-04},

journal = {Frontiers in endocrinology},

volume = {14},

pages = {1234569},

abstract = {Background: Disordered and hypomineralized woven bone formation by dysfunctional mesenchymal stromal cells (MSCs) characterize delayed fracture healing and endocrine -metabolic bone disorders like fibrous dysplasia and Paget disease of bone. To shed light on molecular players in osteoblast differentiation, woven bone formation, and mineralization by MSCs we looked at the intermediate filament desmin (DES) during the skeletogenic commitment of rat bone marrow MSCs (rBMSCs), where its bone-related action remains elusive. Results: Monolayer cultures of immunophenotypically- and morphologically - characterized, adult male rBMSCs showed co-localization of desmin (DES) with vimentin, F-actin, and runx2 in all cell morphotypes, each contributing to sparse and dense colonies. Proteomic analysis of these cells revealed a topologically-relevant interactome, focused on cytoskeletal and related enzymes//chaperone/signalling molecules linking DES to runx2 and alkaline phosphatase (ALP). Osteogenic differentiation led to mineralized woven bone nodules confined to dense colonies, significantly smaller and more circular with respect to controls. It significantly increased also colony-forming efficiency and the number of DES-immunoreactive dense colonies, and immunostaining of co-localized DES/runx-2 and DES/ALP. These data confirmed pre-osteoblastic and osteoblastic differentiation, woven bone formation, and mineralization, supporting DES as a player in the molecular pathway leading to the osteogenic fate of rBMSCs. Conclusion: Immunocytochemical and morphometric studies coupled with proteomic and bioinformatic analysis support the concept that DES may act as an upstream signal for the skeletogenic commitment of rBMSCs. Thus, we suggest that altered metabolism of osteoblasts, woven bone, and mineralization by dysfunctional BMSCs might early be revealed by changes in DES expression//levels. Non-union fractures and endocrine - metabolic bone disorders like fibrous dysplasia and Paget disease of bone might take advantage of this molecular evidence for their early diagnosis and follow-up.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Yb_116,

title = {Discovery of first novel sigma/HDACi dual-ligands with a potent in vitro antiproliferative activity},

author = {Barbaraci C and di Giacomo V and Maruca A and Patamia V and Rocca R and Dichiara M and {Di Rienzo} A and Cacciatore I and Cataldi A and Balaha M and Rapino M and Zagni C and Zampieri D and Pasquinucci L and Parenti C and Amata E and Rescifina A and Alcaro S and Marrazzo A.},

url = {https://www.sciencedirect.com/science/article/pii/S0045206823004558?via%3Dihub},

doi = {10.1016/j.bioorg.2023.106794},

year  = {2023},

date = {2023-10-02},

journal = {Bioorganic chemistry},

volume = {140},

pages = {106794},

abstract = {Designing and discovering compounds for dual-target inhibitors is challenging to synthesize new, safer, and more efficient drugs than single-target drugs, especially to treat multifactorial diseases such as cancer. The simultaneous regulation of multiple targets might represent an alternative synthetic approach to optimize patient compliance and tolerance, minimizing the risk of target-based drug resistance due to the modulation of a few targets. To this end, we conceived for the first time the design and synthesis of dual-ligands σR/HDACi to evaluate possible employment as innovative candidates to address this complex disease. Among all synthesized compounds screened for several tumoral cell lines, compound 6 (Kiσ1R = 38 ± 3.7; Kiσ2R = 2917 ± 769 and HDACs IC50 = 0.59 µM) is the most promising candidate as an antiproliferative agent with an IC50 of 0.9 µM on the HCT116 cell line and no significant toxicity to normal cells. Studies of molecular docking, which confirmed the affinity over σ1R and a pan-HDACs inhibitory behavior, support a possible balanced affinity and activity between both targets.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Y_133,

title = {Aberrant MET activation impairs perinuclear actin cap organization with YAP1 cytosolic relocation},

author = {Sgarzi M and Mazzeschi M and Santi S and Montacci E and Panciera T and Ferlizza E and Girone C and Morselli A and Gelfo V and Kuhre RS and Cavallo C and Valente S and Pasquinelli G and Gyorffy B and D'Uva G and Romaniello D and Lauriola M},

url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10576810/},

doi = {10.1038/s42003-023-05411-y},

year  = {2023},

date = {2023-08-23},

urldate = {2023-08-23},

journal = {Communications biology},

volume = {6},

issue = {1},

pages = {1044},

abstract = {Little is known about the signaling network responsible for the organization of the perinuclear actin cap, a recently identified structure holding unique roles in the regulation of nuclear shape and cell directionality. In cancer cells expressing a constitutively active MET, we show a rearrangement of the actin cap filaments, which crash into perinuclear patches associated with spherical nuclei, meandering cell motility and inactivation of the mechano-transducer YAP1. MET ablation is sufficient to reactivate YAP1 and restore the cap, leading to enhanced directionality and flattened nuclei. Consistently, the introduction of a hyperactive MET in normal epithelial cells, enhances nuclear height and alters the cap organization, as also confirmed by TEM analysis. Finally, the constitutively active YAP1 mutant YAP5SA is able to overcome the effects of oncogenic MET. Overall, our work describes a signaling axis empowering MET-mediated YAP1 dampening and actin cap misalignment, with implications for nuclear shape and cell motility.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Y_129,

title = {Thermostable Lactonases Inhibit Pseudomonas aeruginosa Biofilm: Effect In Vitro and in Drosophila melanogaster Model of Chronic Infection},

author = {Porzio E and Andrenacci D and Manco G},

url = {https://www.mdpi.com/1422-0067/24/23/17028},

doi = {10.3390/ijms242317028},

year  = {2023},

date = {2023-08-18},

journal = {International journal of molecular sciences},

volume = {24},

issue = {23},

pages = {17028},

abstract = {Pseudomonas aeruginosa is one of the six antimicrobial-resistant pathogens known as "ESKAPE" that represent a global threat to human health and are considered priority targets for the development of novel antimicrobials and alternative therapeutics. The virulence of P. aeruginosa is regulated by a four-chemicals communication system termed quorum sensing (QS), and one main class of QS signals is termed acylhomoserine lactones (acyl-HSLs), which includes 3-Oxo-dodecanoil homoserine lactone (3-Oxo-C12-HSL), which regulates the expression of genes implicated in virulence and biofilm formation. Lactonases, like Paraoxonase 2 (PON2) from humans and the phosphotriesterase-like lactonases (PLLs) from thermostable microorganisms, are able to hydrolyze acyl-HSLs. In this work, we explored in vitro and in an animal model the effect of some lactonases on the production of Pseudomonas virulence factors. This study presents a model of chronic infection in which bacteria were administered by feeding, and Drosophila adults were treated with enzymes and the antibiotic tobramycin, alone or in combination. In vitro, we observed significant effects of lactonases on biofilm formation as well as effects on bacterial motility and the expression of virulence factors. The treatment in vivo by feeding with the lactonase SacPox allowed us to significantly increase the biocidal effect of tobramycin in chronic infection.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Yb_115,

title = {Impact of Combined Baricitinib and FTI Treatment on Adipogenesis in Hutchinson-Gilford Progeria Syndrome and Other Lipodystrophic Laminopathies},

author = {Hartinger R and Lederer EM and Schena E and Lattanzi G and Djabali K},

url = {https://www.mdpi.com/2073-4409/12/10/1350},

doi = {10.3390/cells12101350},

year  = {2023},

date = {2023-08-08},

journal = {Cells},

volume = {12},

issue = {10},

pages = {1350},

abstract = {Hutchinson-Gilford progeria syndrome (HGPS) is a rare genetic disease that causes premature aging symptoms, such as vascular diseases, lipodystrophy, loss of bone mineral density, and alopecia. HGPS is mostly linked to a heterozygous and de novo mutation in the LMNA gene (c.1824 C > T; p.G608G), resulting in the production of a truncated prelamin A protein called "progerin". Progerin accumulation causes nuclear dysfunction, premature senescence, and apoptosis. Here, we examined the effects of baricitinib (Bar), an FDA-approved JAK/STAT inhibitor, and a combination of Bar and lonafarnib (FTI) treatment on adipogenesis using skin-derived precursors (SKPs). We analyzed the effect of these treatments on the differentiation potential of SKPs isolated from pre-established human primary fibroblast cultures. Compared to mock-treated HGPS SKPs, Bar and Bar + FTI treatments improved the differentiation of HGPS SKPs into adipocytes and lipid droplet formation. Similarly, Bar and Bar + FTI treatments improved the differentiation of SKPs derived from patients with two other lipodystrophic diseases: familial partial lipodystrophy type 2 (FPLD2) and mandibuloacral dysplasia type B (MADB). Overall, the results show that Bar treatment improves adipogenesis and lipid droplet formation in HGPS, FPLD2, and MADB, indicating that Bar + FTI treatment might further ameliorate HGPS pathologies compared to lonafarnib treatment alone.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Yb_114,

title = {Tissue fluidification promotes a cGAS-STING cytosolic DNA response in invasive breast cancer},

author = {Frittoli E and Palamidessi A and Iannelli F and Zanardi F and Villa S and Barzaghi L and Abdo H and Cancila V and Beznoussenko GV and Della Chiara G and Pagani M and Malinverno C and Bhattacharya D and Pisati F and Yu W and Galimberti V and Bonizzi G and Martini E and Mironov AA and Gioia U and Ascione F and Li Q and Havas K and Magni S and Lavagnino Z and Pennacchio FA and Maiuri P and Caponi S and Mattarelli M and Martino S and {d'Adda di Fagagna F} and Rossi C and Lucioni M and Tancredi R and Pedrazzoli P and Vecchione A and Petrini C and Ferrari F and Lanzuolo C and Bertalot G and Nader G and Foiani M and Piel M and Cerbino R and Giavazzi F and Tripodo C and Scita G },

url = {https://www.nature.com/articles/s41563-022-01431-x},

doi = {10.1038/s41563-022-01431-x},

year  = {2023},

date = {2023-08-08},

journal = {Nature materials},

volume = {22},

issue = {5},

pages = {644-655},

abstract = {The process in which locally confined epithelial malignancies progressively evolve into invasive cancers is often promoted by unjamming, a phase transition from a solid-like to a liquid-like state, which occurs in various tissues. Whether this tissue-level mechanical transition impacts phenotypes during carcinoma progression remains unclear. Here we report that the large fluctuations in cell density that accompany unjamming result in repeated mechanical deformations of cells and nuclei. This triggers a cellular mechano-protective mechanism involving an increase in nuclear size and rigidity, heterochromatin redistribution and remodelling of the perinuclear actin architecture into actin rings. The chronic strains and stresses associated with unjamming together with the reduction of Lamin B1 levels eventually result in DNA damage and nuclear envelope ruptures, with the release of cytosolic DNA that activates a cGAS-STING (cyclic GMP-AMP synthase-signalling adaptor stimulator of interferon genes)-dependent cytosolic DNA response gene program. This mechanically driven transcriptional rewiring ultimately alters the cell state, with the emergence of malignant traits, including epithelial-to-mesenchymal plasticity phenotypes and chemoresistance in invasive breast carcinoma.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Yb__109,

title = {The Effect of Crackers Enriched with Camelina Sativa Oil on Omega-3 Serum Fatty Acid Composition in Older Adults: A Randomized Placebo-Controlled Pilot Trial},

author = {De Giuseppe R and Di Napoli I and Tomasinelli CE and Vincenti A and Biino G and Sommella E and Ferron L and Campiglia P and Ferrara F and Casali PM and Cena H



},

url = {https://link.springer.com/article/10.1007/s12603-023-1925-x},

doi = {10.1007/s12603-023-1925-x},

year  = {2023},

date = {2023-08-08},

journal = {Journal of nutrition health & aging},

volume = {27},

number = {463-471},

issue = {6},

abstract = {Background: Camelina sativa oil is one of the richest dietary sources of omega-3, with polyunsaturated fatty acids amounts of over 50%, linolenic acid content of around 40-45%, and linoleic acid of about 15%. Moreover, this oil is a valuable source of antioxidants which provide oxidative stability. All those features raise interest in considering Camelina oil as an alternative and sustainable oil source providing stable omega-3-rich emulsions for functional food production. Objectives: The present study aimed to investigate the effects of Camelina oil-enriched crackers on serum omega-3 concentration, inflammatory markers and serum lipid profile. Design: Randomized placebo-controlled pilot trial. Setting: Research and Development Center (Complife Italia s.r.l.). Participants: Sixty-six free-living older volunteers (aged≥65 years). Intervention: Older adults were enrolled and randomly assigned to one of two groups: the camelina group or the placebo group. Subjects consumed daily 35 g of crackers (Camelina enriched crackers or placebo ones) twice daily for 12 weeks. Measurements: Serum polyunsaturated fatty acid profile, inflammatory status and serum lipid panel parameters were recorded pre and post-intervention. Results: In the camelina group, alpha-linolenic acid serum concentration was significantly higher (p<0.01) compared to the placebo group at the end of the study. Concerning inflammatory plasma markers, a significant mean pro-inflammatory interleukin-18 plasma concentration decrease in the placebo group compared to the camelina one was observed (p<0.05). No significant differences in other mean inflammatory markers concentrations post-intervention were noted in either group. Lastly, examining the change in lipid profile, it is noteworthy that a higher reduction of total cholesterol, low-density lipoprotein and triglycerides in the camelina group post-intervention, despite the lack of statistical significance. Conclusion: Camelina oil significantly elevated the serum alpha-linolenic acid concentration with no significant changes in inflammatory markers and lipid profile. Trial registration: ClinicalTrials.gov NCT04965948.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Yb_112,

title = {Targeting the Interplay of Independent Cellular Pathways and Immunity: A Challenge in Cancer Immunotherapy},

author = {Lauriola A and Davalli P and Marverti G and Santi S and Caporali A and D'Arca D},

url = {https://www.mdpi.com/2072-6694/15/11/3009},

doi = {10.3390/cancers15113009},

year  = {2023},

date = {2023-08-08},

journal = {Cancers-Basel},

volume = {15},

issue = {11},

pages = {3009},

abstract = {Immunotherapy is a cancer treatment that exploits the capacity of the body's immune system to prevent, control, and remove cancer. Immunotherapy has revolutionized cancer treatment and significantly improved patient outcomes for several tumor types. However, most patients have not benefited from such therapies yet. Within the field of cancer immunotherapy, an expansion of the combination strategy that targets independent cellular pathways that can work synergistically is predicted. Here, we review some consequences of tumor cell death and increased immune system engagement in the modulation of oxidative stress and ubiquitin ligase pathways. We also indicate combinations of cancer immunotherapies and immunomodulatory targets. Additionally, we discuss imaging techniques, which are crucial for monitoring tumor responses during treatment and the immunotherapy side effects. Finally, the major outstanding questions are also presented, and directions for future research are described.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Yb_111,

title = {Sustained oral spermidine supplementation rescues functional and structural defects in COL6-deficient myopathic mice},

author = {Gambarotto L and Metti S and Corpetti M and Baraldo M and Sabatelli P and Castagnaro S and Cescon M and Blaauw B and Bonaldo P },

url = {https://www.tandfonline.com/doi/abs/10.1080/15548627.2023.2241125},

doi = {10.1080/15548627.2023.2241125},

year  = {2023},

date = {2023-08-08},

urldate = {2023-08-08},

journal = {Autophagy},

volume = {19},

issue = {12},

pages = {3221-3229},

abstract = {COL6 (collagen type VI)-related myopathies (COL6-RM) are a distinct group of inherited muscle disorders caused by mutations of COL6 genes and characterized by early-onset muscle weakness, for which no cure is available yet. Key pathophysiological features of COL6-deficient muscles involve impaired macroautophagy/autophagy, mitochondrial dysfunction, neuromuscular junction fragmentation and myofiber apoptosis. Targeting autophagy by dietary means elicited beneficial effects in both col6a1 null (col6a1-/-) mice and COL6-RM patients. We previously demonstrated that one-month per os administration of the nutraceutical spermidine reactivates autophagy and ameliorates myofiber defects in col6a1-/- mice but does not elicit functional improvement. Here we show that a 100-day-long spermidine regimen is able to rescue muscle strength in col6a1-/- mice, with also a beneficial impact on mitochondria and neuromuscular junction integrity, without any noticeable side effects. Altogether, these data provide a rationale for the application of spermidine in prospective clinical trials for COL6-RM.Abbreviations: AChR: acetylcholine receptor; BTX: bungarotoxin; CNF: centrally nucleated fibers; Colch: colchicine; COL6: collagen type VI; COL6-RM: COL6-related myopathies; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; NMJ: neuromuscular junction; Spd: spermidine; SQSTM1/p62: sequestosome 1; TA: tibialis anterior; TOMM20: translocase of outer mitochondrial membrane 20; TUNEL: terminal deoxynucleotidyl transferase dUTP-mediated nick-end labeling.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Yb_110,

title = {Single Cell Determination of 7,8-dihydro-8-oxo-2′-deoxyguanosine by Fluorescence Techniques: Antibody vs. Avidin Labeling},

author = {Maraventano G and Ticli G and Cazzalini O and Stivala LA and Ramos-Gonzalez M and Rodríguez JL and Prosperi E},

url = {https://www.mdpi.com/1420-3049/28/11/4326},

doi = {10.3390/molecules28114326},

year  = {2023},

date = {2023-08-08},

journal = {Molecules},

volume = {28},

issue = {11},

pages = {4326},

abstract = {An important biomarker of oxidative damage in cellular DNA is the formation of 7,8-dihydro-8-oxo-2′-deoxyguanosine (8-oxodG). Although several methods are available for the biochemical analysis of this molecule, its determination at the single cell level may provide significant advantages when investigating the influence of cell heterogeneity and cell type in the DNA damage response. to. For this purpose, antibodies recognizing 8-oxodG are available; however, detection with the glycoprotein avidin has also been proposed because of a structural similarity between its natural ligand biotin and 8-oxodG. Whether the two procedures are equivalent in terms of reliability and sensitivity is not clear. In this study, we compared the immunofluorescence determination of 8-oxodG in cellular DNA using the monoclonal antibody N45.1 and labeling using avidin conjugated with the fluorochrome Alexa Fluor488 (AF488). Oxidative DNA damage was induced in different cell types by treatment with potassium bromate (KBrO3), a chemical inducer of reactive oxygen species (ROS). By using increasing concentrations of KBrO3, as well as different reaction conditions, our results indicate that the monoclonal antibody N45.1 provides a specificity of 8-oxodG labeling greater than that attained with avidin-AF488. These findings suggest that immunofluorescence techniques are best suited to the in situ analysis of 8-oxodG as a biomarker of oxidative DNA damage.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Yb_109,

title = {Sen1 and Rrm3 ensure permissive topological conditions for replication termination},

author = {Choudhary R and Niska-Blakie J and Adhil M and Liberi G and Achar YJ and Giannattasio M and Foiani M},

url = {https://www.sciencedirect.com/science/article/pii/S2211124723007581?via%3Dihub},

doi = {10.1016/j.celrep.2023.112747},

year  = {2023},

date = {2023-08-08},

journal = {Cell reports},

volume = {42},

issue = {7},

pages = {112747},

abstract = {Replication forks terminate at TERs and telomeres. Forks that converge or encounter transcription generate topological stress. Combining genetics, genomics, and transmission electron microscopy, we find that Rrm3hPif1 and Sen1hSenataxin helicases assist termination at TERs; Sen1 specifically acts at telomeres. rrm3 and sen1 genetically interact and fail to terminate replication, exhibiting fragility at termination zones (TERs) and telomeres. sen1rrm3 accumulates RNA-DNA hybrids and X-shaped gapped or reversed converging forks at TERs; sen1, but not rrm3, builds up RNA polymerase II (RNPII) at TERs and telomeres. Rrm3 and Sen1 restrain Top1 and Top2 activities, preventing toxic accumulation of positive supercoil at TERs and telomeres. We suggest that Rrm3 and Sen1 coordinate the activities of Top1 and Top2 when forks encounter transcription head on or codirectionally, respectively, thus preventing the slowing down of DNA and RNA polymerases. Hence Rrm3 and Sen1 are indispensable to generate permissive topological conditions for replication termination.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Y,

title = {SARS-CoV-2 infection induces DNA damage, through CHK1 degradation and impaired 53BP1 recruitment, and cellular senescence},

author = {Gioia U and Tavella S and Martínez-Orellana P and Cicio G and Colliva A and Ceccon M and Cabrini M and Henriques AC and Fumagalli V and Paldino A and Presot E and Rajasekharan S and Iacomino N and Pisati F and Matti V and Sepe S and Conte MI and Barozzi S and Lavagnino Z and Carletti T and Volpe MC and Cavalcante P and Iannacone M and Rampazzo C and Bussani R and Tripodo C and Zacchigna S and Marcello A and {d'Adda di Fagagna F} },

url = {https://www.nature.com/articles/s41556-023-01096-x},

doi = {10.1038/s41556-023-01096-x},

year  = {2023},

date = {2023-08-08},

urldate = {2023-08-08},

journal = {Nature cell biology},

volume = {25},

issue = {4},

pages = {550-564},

abstract = {Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the RNA virus responsible for the coronavirus disease 2019 (COVID-19) pandemic. Although SARS-CoV-2 was reported to alter several cellular pathways, its impact on DNA integrity and the mechanisms involved remain unknown. Here we show that SARS-CoV-2 causes DNA damage and elicits an altered DNA damage response. Mechanistically, SARS-CoV-2 proteins ORF6 and NSP13 cause degradation of the DNA damage response kinase CHK1 through proteasome and autophagy, respectively. CHK1 loss leads to deoxynucleoside triphosphate (dNTP) shortage, causing impaired S-phase progression, DNA damage, pro-inflammatory pathways activation and cellular senescence. Supplementation of deoxynucleosides reduces that. Furthermore, SARS-CoV-2 N-protein impairs 53BP1 focal recruitment by interfering with damage-induced long non-coding RNAs, thus reducing DNA repair. Key observations are recapitulated in SARS-CoV-2-infected mice and patients with COVID-19. We propose that SARS-CoV-2, by boosting ribonucleoside triphosphate levels to promote its replication at the expense of dNTPs and by hijacking damage-induced long non-coding RNAs' biology, threatens genome integrity and causes altered DNA damage response activation, induction of inflammation and cellular senescence.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Yb_108,

title = {Ribosomal Dysfunction Is a Common Pathomechanism in Different Forms of Trichothiodystrophy},

author = {Zhu G and Khalid F and Zhang D and Cao Z and Maity P and Kestler HA and Orioli D and Scharffetter-Kochanek K and Iben S},

url = {https://www.mdpi.com/2073-4409/12/14/1877},

doi = {10.3390/cells12141877},

year  = {2023},

date = {2023-08-08},

journal = {Cells},

volume = {12},

issue = {14},

pages = {1877},

abstract = {Mutations in a broad variety of genes can provoke the severe childhood disorder trichothiodystrophy (TTD) that is classified as a DNA repair disease or a transcription syndrome of RNA polymerase II. In an attempt to identify the common underlying pathomechanism of TTD we performed a knockout/knockdown of the two unrelated TTD factors TTDN1 and RNF113A and investigated the consequences on ribosomal biogenesis and performance. Interestingly, interference with these TTD factors created a nearly uniform impact on RNA polymerase I transcription with downregulation of UBF, disturbed rRNA processing and reduction of the backbone of the small ribosomal subunit rRNA 18S. This was accompanied by a reduced quality of decoding in protein translation and the accumulation of misfolded and carbonylated proteins, indicating a loss of protein homeostasis (proteostasis). As the loss of proteostasis by the ribosome has been identified in the other forms of TTD, here we postulate that ribosomal dysfunction is a common underlying pathomechanism of TTD.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Yb_107,

title = {Phospholipase Family Enzymes in Lung Cancer: Looking for Novel Therapeutic Approaches},

author = {Salucci S and Aramini B and Bartoletti-Stella A and Versari I and Martinelli G and Blalock WL and Stella F and Faenza I},

url = {https://www.mdpi.com/2072-6694/15/12/3245},

doi = {10.3390/cancers15123245},

year  = {2023},

date = {2023-08-08},

journal = {Cancers-Basel},

volume = {15},

issue = {12},

pages = {3245},

abstract = {Lung cancer (LC) is the second most common neoplasm in men and the third most common in women. In the last decade, LC therapies have undergone significant improvements with the advent of immunotherapy. However, the effectiveness of the available treatments remains insufficient due to the presence of therapy-resistant cancer cells. For decades, chemotherapy and radiotherapy have dominated the treatment strategy for LC; however, relapses occur rapidly and result in poor survival. Malignant lung tumors are classified as either small- or non-small-cell lung carcinoma (SCLC and NSCLC). Despite improvements in the treatment of LC in recent decades, the benefits of surgery, radiotherapy, and chemotherapy are limited, although they have improved the prognosis of LC despite the persistent low survival rate due to distant metastasis in the late stage. The identification of novel prognostic molecular markers is crucial to understand the underlying mechanisms of LC initiation and progression. The potential role of phosphatidylinositol in tumor growth and the metastatic process has recently been suggested by some researchers. Phosphatidylinositols are lipid molecules and key players in the inositol signaling pathway that have a pivotal role in cell cycle regulation, proliferation, differentiation, membrane trafficking, and gene expression. In this review, we discuss the current understanding of phosphoinositide-specific phospholipase enzymes and their emerging roles in LC.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Yb_105,

title = {MetChem: a new pipeline to explore structural similarity across metabolite modules},

author = {Abdel-Shafy EA and Melak T and MacIntyre DA and Zadra G and Zerbini LF and Piazza S and Cacciatore S},

url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10322652/},

doi = {10.1093/bioadv/vbad053},

year  = {2023},

date = {2023-08-08},

journal = {Bioinformatics advances},

volume = {3},

issue = {1},

abstract = {Computational analysis and interpretation of metabolomic profiling data remains a major challenge in translational research. Exploring metabolic biomarkers and dysregulated metabolic pathways associated with a patient phenotype could offer new opportunities for targeted therapeutic intervention. Metabolite clustering based on structural similarity has the potential to uncover common underpinnings of biological processes. To address this need, we have developed the MetChem package. MetChem is a quick and simple tool that allows to classify metabolites in structurally related modules, thus revealing their functional information.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Yb_104,

title = {MCD Diet Modulates HuR and Oxidative Stress-Related HuR Targets in Rats},

author = {Ferrigno A and Campagnoli LIM and Barbieri A and Marchesi N and Pascale A and Croce AC and Vairetti M and Di Pasqua LG},

url = {https://www.mdpi.com/1422-0067/24/12/9808},

doi = {10.3390/ijms24129808},

year  = {2023},

date = {2023-08-08},

journal = {International journal of molecular sciences},

volume = {24},

issue = {12},

pages = {9808},

abstract = {The endogenous antioxidant defense plays a big part in the pathogenesis of non-alcoholic fatty liver disease (NAFLD), a common metabolic disorder that can lead to serious complications such as cirrhosis and cancer. HuR, an RNA-binding protein of the ELAV family, controls, among others, the stability of MnSOD and HO-1 mRNA. These two enzymes protect the liver cells from oxidative damage caused by excessive fat accumulation. Our aim was to investigate the expression of HuR and its targets in a methionine-choline deficient (MCD) model of NAFLD. To this aim, we fed male Wistar rats with an MCD diet for 3 and 6 weeks to induce NAFLD; then, we evaluated the expression of HuR, MnSOD, and HO-1. The MCD diet induced fat accumulation, hepatic injury, oxidative stress, and mitochondrial dysfunction. A HuR downregulation was also observed in association with a reduced expression of MnSOD and HO-1. Moreover, the changes in the expression of HuR and its targets were significantly correlated with oxidative stress and mitochondrial injury. Since HuR plays a protective role against oxidative stress, targeting this protein could be a therapeutic strategy to both prevent and counteract NAFLD.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Yb_103,

title = {Lipid metabolism dysfunction following symbiont elimination is linked to altered Kennedy pathway homeostasis},

author = {Attardo GM and Benoit JB and Michalkova V and Kondragunta A and Baumann AA and Weiss BL and Malacrida A and Scolari F and Aksoy S },

url = {https://www.sciencedirect.com/science/article/pii/S2589004223011859?via%3Dihub},

doi = {10.1016/j.isci.2023.107108},

year  = {2023},

date = {2023-08-08},

journal = {iScience},

volume = {26},

issue = {7},

pages = {107108},

abstract = {Lipid metabolism is critical for insect reproduction, especially for species that invest heavily in the early developmental stages of their offspring. The role of symbiotic bacteria during this process is understudied but likely essential. We examined the role of lipid metabolism during the interaction between the viviparous tsetse fly (Glossina morsitans morsitans) and its obligate endosymbiotic bacteria (Wigglesworthia glossinidia) during tsetse pregnancy. We observed increased CTP:phosphocholine cytidylyltransferase (cct1) expression during pregnancy, which is critical for phosphatidylcholine biosynthesis in the Kennedy pathway. Experimental removal of Wigglesworthia impaired lipid metabolism via disruption of the Kennedy pathway, yielding obese mothers whose developing progeny starve. Functional validation via experimental cct1 suppression revealed a phenotype similar to females lacking obligate Wigglesworthia symbionts. These results indicate that, in Glossina, symbiont-derived factors, likely B vitamins, are critical for the proper function of both lipid biosynthesis and lipolysis to maintain tsetse fly fecundity.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Yb_102,

title = {Lactate as Key Metabolite in Prostate Cancer Progression: What Are the Clinical Implications?},

author = {Chetta P and Sriram R and Zadra G},

url = {https://www.mdpi.com/2072-6694/15/13/3473},

doi = {Cancers-Basel},

year  = {2023},

date = {2023-08-08},

journal = {Cancers - Basel},

volume = {15},

issue = {13},

pages = {3473},

abstract = {Advanced prostate cancer represents the fifth leading cause of cancer death in men worldwide. Although androgen-receptor signaling is the major driver of the disease, evidence is accumulating that disease progression is supported by substantial metabolic changes. Alterations in de novo lipogenesis and fatty acid catabolism are consistently reported during prostate cancer development and progression in association with androgen-receptor signaling. Therefore, the term "lipogenic phenotype" is frequently used to describe the complex metabolic rewiring that occurs in prostate cancer. However, a new scenario has emerged in which lactate may play a major role. Alterations in oncogenes/tumor suppressors, androgen signaling, hypoxic conditions, and cells in the tumor microenvironment can promote aerobic glycolysis in prostate cancer cells and the release of lactate in the tumor microenvironment, favoring immune evasion and metastasis. As prostate cancer is composed of metabolically heterogenous cells, glycolytic prostate cancer cells or cancer-associated fibroblasts can also secrete lactate and create "symbiotic" interactions with oxidative prostate cancer cells via lactate shuttling to sustain disease progression. Here, we discuss the multifaceted role of lactate in prostate cancer progression, taking into account the influence of the systemic metabolic and gut microbiota. We call special attention to the clinical opportunities of imaging lactate accumulation for patient stratification and targeting lactate metabolism.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Yb__97,

title = {Interaction of SARS-CoV-2 Nucleocapsid Protein and Human RNA Helicases DDX1 and DDX3X Modulates Their Activities on Double-Stranded RNA},

author = {Lodola C and Secchi M and Sinigiani V and De Palma A and Rossi R and Perico D and Mauri PL and Maga G},

url = {https://www.mdpi.com/1422-0067/24/6/5784},

doi = {10.3390/ijms24065784},

year  = {2023},

date = {2023-08-08},

journal = {International journal of molecular sciences},

volume = {24},

issue = {6},

pages = {5784},

abstract = {The nucleocapsid protein Np of SARS-CoV-2 is involved in the replication, transcription, and packaging of the viral genome, but it also plays a role in the modulation of the host cell innate immunity and inflammation response. Ectopic expression of Np alone was able to induce significant changes in the proteome of human cells. The cellular RNA helicase DDX1 was among the proteins whose levels were increased by Np expression. DDX1 and its related helicase DDX3X were found to physically interact with Np and to increase 2- to 4-fold its affinity for double-stranded RNA in a helicase-independent manner. Conversely, Np inhibited the RNA helicase activity of both proteins. These functional interactions among Np and DDX1 and DDX3X highlight novel possible roles played by these host RNA helicases in the viral life cycle.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Yb_100,

title = {Immunoelectron Microscopy Methods},

author = {Squarzoni S},

url = {https://link.springer.com/protocol/10.1007/978-1-0716-3143-0_15},

doi = {10.1007/978-1-0716-3143-0_15},

year  = {2023},

date = {2023-08-08},

journal = {Methods in molecular biology},

volume = {2655},

pages = {201-210},

abstract = {"Immunoelectron microscopy" defines a group of techniques developed for visualizing where components of cells or tissues are localized, by means of a transmission electron microscope (TEM) at a subcellular resolution. The method is based on antigen recognition by primary antibodies and subsequent visualization of recognized structures by means of electron-opaque gold granules, which are easily visible in TEM images. The potentially high resolution of this method relies on the very small size of the colloidal gold label, which consists of granules ranging from 1 to 60 nm in diameter, mostly used in the 5-15 nm sizes.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Yb_99,

title = {Identification of bi-allelic LFNG variants in three patients and further clinical and molecular refinement of spondylocostal dysostosis 3},

author = {Lecca M and Bedeschi MF and Izzi C and Dordoni C and Rinaldi B and Peluso F and Caraffi SG and Prefumo F and Signorelli M and Zanzucchi M and Bione S and Ghigna C and Sassi S and Novelli A and Valente EM and Superti-Furga A and Garavelli L and Errichiello E },

url = {https://onlinelibrary.wiley.com/doi/10.1111/cge.14336},

doi = {10.1111/cge.14336},

year  = {2023},

date = {2023-08-08},

journal = {Clinical genetics},

volume = {104},

issue = {2},

pages = {230},

abstract = {Spondylocostal dysostosis (SCD), a condition characterized by multiple segmentation defects of the vertebrae and rib malformations, is caused by bi-allelic variants in one of the genes involved in the Notch signaling pathway that tunes the ""segmentation clock"" of somitogenesis: DLL3, HES7, LFNG, MESP2, RIPPLY2, and TBX6. To date, seven individuals with LFNG variants have been reported in the literature. In this study we describe two newborns and one fetus with SCD, who were found by trio-based exome sequencing (trio-ES) to carry homozygous (c.822-5C>T) or compound heterozygous (c.[863dup];[1063G>A]) and (c.[521G>T];[890T>G]) variants in LFNG. Notably, the c.822-5C>T change, affecting the polypyrimidine tract of intron 5, is the first non-coding variant reported in LFNG. This study further refines the clinical and molecular features of spondylocostal dysostosis 3 and adds to the numerous investigations supporting the usefulness of trio-ES approach in prenatal and neonatal settings.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Yb_98,

title = {Identification and Biological Characterization of the Pyrazolo[3,4- d]pyrimidine Derivative SI388 Active as Src Inhibitor},

author = {Contadini C and Cirotti C and Carbone A and Norouzi M and Cianciusi A and Crespan E and Perini C and Maga G and Barilà D and Musumeci F and Schenone S},

url = {https://www.mdpi.com/1424-8247/16/7/958},

doi = {10.3390/ph16070958},

year  = {2023},

date = {2023-08-08},

journal = {Pharmaceuticals - Basel},

volume = {16},

issue = {7},

pages = {958},

abstract = {Src is a non-receptor tyrosine kinase (TK) whose involvement in cancer, including glioblastoma (GBM), has been extensively demonstrated. In this context, we started from our in-house library of pyrazolo[3,4-d]pyrimidines that are active as Src and/or Bcr-Abl TK inhibitors and performed a lead optimization study to discover a new generation derivative that is suitable for Src kinase targeting. We synthesized a library of 19 compounds, 2a-s. Among these, compound 2a (SI388) was identified as the most potent Src inhibitor. Based on the cell-free results, we investigated the effect of SI388 in 2D and 3D GBM cellular models. Interestingly, SI388 significantly inhibits Src kinase, and therefore affects cell viability, tumorigenicity and enhances cancer cell sensitivity to ionizing radiation.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Yb_97,

title = {Hyperextended telomeres promote formation of C-circle DNA in telomerase positive human cells},

author = {Jones CY and Williams CL and Moreno SP and Morris DK and Mondello C and Karlseder J and Bertuch AA},

url = {https://www.sciencedirect.com/science/article/pii/S0021925823003071?via%3Dihub},

doi = {10.1016/j.jbc.2023.104665},

year  = {2023},

date = {2023-08-08},

urldate = {2023-08-08},

journal = {Journal of biological chemistry},

volume = {299},

issue = {5},

pages = {104665},

abstract = {Telomere length maintenance is crucial to cancer cell immortality. Up to 15% of cancers utilize a telomerase-independent, recombination-based mechanism termed alternative lengthening of telomeres (ALT). Currently, the primary ALT biomarker is the C-circle, a type of circular DNA with extrachromosomal telomere repeats (cECTRs). How C-circles form is not well characterized. We investigated C-circle formation in the human cen3tel cell line, a long-telomere, telomerase+ (LTT+) cell line with progressively hyper-elongated telomeres (up to ∼100 kb). cECTR signal was observed in 2D gels and C-circle assays but not t-circle assays, which also detect cECTRs. Telomerase activity and C-circle signal were not separable in the analysis of clonal populations, consistent with C-circle production occurring within telomerase+ cells. We observed similar cECTR results in two other LTT+ cell lines, HeLa1.3 (∼23 kb telomeres) and HeLaE1 (∼50 kb telomeres). In LTT+ cells, telomerase activity did not directly impact C-circle signal; instead, C-circle signal correlated with telomere length. LTT+ cell lines were less sensitive to hydroxyurea than ALT+ cell lines, suggesting that ALT status is a stronger contributor to replication stress levels than telomere length. Additionally, the DNA repair-associated protein FANCM did not suppress C-circles in LTT+ cells as it does in ALT+ cells. Thus, C-circle formation may be driven by telomere length, independently of telomerase and replication stress, highlighting limitations of C-circles as a stand-alone ALT biomarker.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Yb_96,

title = {Hydrogen Sulfide (H2S): As A Potent Modulator And Therapeutic Prodrug In Cancer},

author = {Faris P and Negri S and Faris D and Scolari F and Montagna D and Moccia F },

url = {https://www.eurekaselect.com/article/129095},

doi = {10.2174/0929867330666230126100638},

year  = {2023},

date = {2023-08-08},

journal = {Current medicinal chemistry},

volume = {30},

issue = {40},

pages = {4506-4532},

abstract = {Hydrogen sulfide (H2S) is an endogenous gaseous molecule present in all living organisms and has been traditionally studied for its toxicity. Interestingly, increased understanding of H2S effects in organ physiology has recently shown its relevance as a signalling molecule, with potentially important implications in variety of clinical disorders, including cancer. H2S is primarily produced in mammalian cells under various enzymatic pathways. A developing focus of H2S is a blooming hotspot that studies chemical, biological mechanisms, and therapeutic effects of H2S. Herein, we describe the physiological and biochemical properties of H2S, the enzymatic pathways leading to its endogenous production and its catabolic routes. In addition, we discuss the role of currently known H2S-releasing agents, or H2S donors, including their potential as therapeutic tools. Then we illustrate the mechanisms known to support the pleiotropic effects of H2S, with a particular focus on persulfhydration, which plays a key role in H2S-mediating signalling pathways. We then address the paradoxical role played by H2S in tumour biology and discuss the potential of exploiting H2S levels as novel cancer biomarkers and diagnostic tools. Finally, we describe the most recent preclinical applications focused on assessing the anti-cancer impact of most common H2S-releasing compounds. While the evidence in favour of H2S as an alternative cancer therapy in the field of translational medicine is yet to be clearly provided, application of H2S is emerging as potent anticancer therapies in preclinical trails.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Yb_95,

title = {Fatty Acids and Bilirubin as Intrinsic Autofluorescence Serum Biomarkers of Drug Action in a Rat Model of Liver Ischemia and Reperfusion},

author = {Croce AC and Ferrigno A and Palladini G and Mannucci B and Vairetti M and Di Pasqua LG},

url = {https://www.mdpi.com/1420-3049/28/9/3818},

doi = {10.3390/molecules28093818},

year  = {2023},

date = {2023-08-08},

journal = {Molecules},

volume = {28},

issue = {9},

pages = {3818},

abstract = {The autofluorescence of specific fatty acids, retinoids, and bilirubin in crude serum can reflect changes in liver functional engagement in maintaining systemic metabolic homeostasis. The role of these fluorophores as intrinsic biomarkers of pharmacological actions has been investigated here in rats administered with obeticholic acid (OCA), a Farnesoid-X Receptor (FXR) agonist, proven to counteract the increase of serum bilirubin in hepatic ischemia/reperfusion (I/R) injury. Fluorescence spectroscopy has been applied to an assay serum collected from rats submitted to liver I/R (60/60 min ± OCA administration). The I/R group showed changes in the amplitude and profiles of emission spectra excited at 310 or 366 nm, indicating remarkable alterations in the retinoid and fluorescing fatty acid balance, with a particular increase in arachidonic acid. The I/R group also showed an increase in bilirubin AF, detected in the excitation spectra recorded at 570 nm. OCA greatly reversed the effects observed in the I/R group, confirmed by the biochemical analysis of bilirubin and fatty acids. These results are consistent with a relationship between OCA anti-inflammatory effects and the acknowledged roles of fatty acids as precursors of signaling agents mediating damaging responses to harmful stimuli, supporting serum autofluorescence analysis as a possible direct, real-time, cost-effective tool for pharmacological investigations.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Yb_94,

title = {Collagen VI in the Musculoskeletal System},

author = {Di Martino A and Cescon M and D'Agostino C and Schilardi F and Sabatelli P and Merlini L and Faldini C},

url = {https://www.mdpi.com/1422-0067/24/6/5095},

doi = {10.3390/ijms24065095},

year  = {2023},

date = {2023-08-08},

journal = {International journal of molecular sciences},

volume = {24},

issue = {6},

pages = {5095},

abstract = {Collagen VI exerts several functions in the tissues in which it is expressed, including mechanical roles, cytoprotective functions with the inhibition of apoptosis and oxidative damage, and the promotion of tumor growth and progression by the regulation of cell differentiation and autophagic mechanisms. Mutations in the genes encoding collagen VI main chains, COL6A1, COL6A2 and COL6A3, are responsible for a spectrum of congenital muscular disorders, namely Ullrich congenital muscular dystrophy (UCMD), Bethlem myopathy (BM) and myosclerosis myopathy (MM), which show a variable combination of muscle wasting and weakness, joint contractures, distal laxity, and respiratory compromise. No effective therapeutic strategy is available so far for these diseases; moreover, the effects of collagen VI mutations on other tissues is poorly investigated. The aim of this review is to outline the role of collagen VI in the musculoskeletal system and to give an update about the tissue-specific functions revealed by studies on animal models and from patients' derived samples in order to fill the knowledge gap between scientists and the clinicians who daily manage patients affected by collagen VI-related myopathies.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Yb_93,

title = {Characterization of Spontaneous Melanization by Fluorescence Spectroscopy: A Basis for Analytical Application to Biological Substrates},

author = {Croce AC and Scolari F},

url = {https://www.mdpi.com/2079-7737/12/3/433},

doi = {10.3390/biology12030433},

year  = {2023},

date = {2023-08-08},

journal = {Biology-Basel},

volume = {12},

issue = {3},

pages = {433},

abstract = {Melanin is present in various biological substrates where it may participate in several processes, from innate immunity to the still-unsolved opposite roles in antioxidant protection, including photoprotection and the related ability to interact with light. Melanin-light interaction has also been an important source of inspiration for the development of innovative bioengineering applications. These are based on melanin's light-energy-absorption ability of its chemically and structurally complex components and precursors, and on the improvement in analytical and diagnostic procedures in biomedicine. In this regard, here, we characterized the fluorescence spectral properties of melanin and of its precursor L-tyrosine in an aqueous solution during spontaneous melanization. Besides the confirmation of the typical fluorescence-emission signature of melanin and L-tyrosine, we provide additional insights on both emission and excitation spectra recorded during melanization. On these bases, we performed a subsequent characterization on the aqueous extracts from two different melanin-containing biological substrates, namely hairs from a domestic black cat and eggs from the Asian tiger mosquito. The results from the mild extraction procedure, purposely applied to obtain only the soluble components, combined with fluorescence spectral analysis are expected to promote further investigation of the melanization processes, particularly in insects.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Yb_92,

title = {ARID1A in cancer: Friend or foe?},

author = {Fontana B and Gallerani G and Salamon I and Pace I and Roncarati R and Ferracin M },

url = {https://www.frontiersin.org/articles/10.3389/fonc.2023.1136248/full},

doi = {10.3389/fonc.2023.1136248},

year  = {2023},

date = {2023-08-08},

journal = {Frontiers in Oncology},

volume = {13},

pages = {1136248},

abstract = {ARID1A belongs to a class of chromatin regulatory proteins that function by maintaining accessibility at most promoters and enhancers, thereby regulating gene expression. The high frequency of ARID1A alterations in human cancers has highlighted its significance in tumorigenesis. The precise role of ARID1A in cancer is highly variable since ARID1A alterations can have a tumor suppressive or oncogenic role, depending on the tumor type and context. ARID1A is mutated in about 10% of all tumor types including endometrial, bladder, gastric, liver, biliopancreatic cancer, some ovarian cancer subtypes, and the extremely aggressive cancers of unknown primary. Its loss is generally associated with disease progression more often than onset. In some cancers, ARID1A loss is associated with worse prognostic features, thus supporting a major tumor suppressive role. However, some exceptions have been reported. Thus, the association of ARID1A genetic alterations with patient prognosis is controversial. However, ARID1A loss of function is considered conducive for the use of inhibitory drugs which are based on synthetic lethality mechanisms. In this review we summarize the current knowledge on the role of ARID1A as tumor suppressor or oncogene in different tumor types and discuss the strategies for treating ARID1A mutated cancers.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Yb_,

title = {Antitumor activity of natural pigment violacein against osteosarcoma and rhabdomyosarcoma cell lines},

author = {Milosevic E and Stanisavljevic N and Boskovic S and Stamenkovic N and Novkovic M and Bavelloni A and Cenni V and Kojic S and Jasnic J},

url = {https://link.springer.com/article/10.1007/s00432-023-04930-9},

doi = {10.1007/s00432-023-04930-9},

year  = {2023},

date = {2023-08-07},

urldate = {2023-08-07},

journal = {Journal of cancer research and clinical oncology},

volume = {149},

issue = {13},

pages = {10957-10987},

abstract = {Purpose: Sarcomas are rare and heterogenic tumors with unclear etiology. They develop in bone and connective tissue, mainly in pediatric patients. To increase efficacy of current therapeutic options, natural products showing selective toxicity to tumor cells are extensively investigated. Here, we evaluated antitumor activity of bacterial pigment violacein in osteosarcoma (OS) and rhabdomyosarcoma (RMS) cell lines. Methods: The toxicity of violacein was assessed in vitro and in vivo, using MTT assay and FET test. The effect of violacein on cell migration was monitored by wound healing assay, cell death by flow cytometry, uptake of violacein by fluorescence microscopy, generation of reactive oxygen species (ROS) by DCFH-DA assay and lipid peroxidation by TBARS assay. Results: Violacein IC50 values for OS and RMS cells were in a range from 0.35 to 0.88 µM. Its selectivity toward malignant phenotype was confirmed on non-cancer V79-4 cells, and it was safe in vivo, for zebrafish embryos in doses up to 1 µM. Violacein induced apoptosis and affected the migratory potential of OS and RMS cells. It was found on the surfaces of tested cells. Regarding the mechanism of action, violacein acted on OS and RMS cells independently of oxidative signaling, as judged by no increase in intracellular ROS generation and no lipid peroxidation. Conclusion: Our study provided further evidence that reinforces the potential of violacein as an anticancer agent and candidate to consider for improvement of the effectiveness of traditional OS and RMS therapies.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Yb_90,

title = {Alternative Splicing, RNA Editing, and the Current Limits of Next Generation Sequencing},

author = {Piazzi M and Bavelloni A and Salucci S and Faenza I and Blalock WL},

url = {https://www.mdpi.com/2073-4425/14/7/1386},

doi = {10.3390/genes14071386},

year  = {2023},

date = {2023-08-07},

journal = {Genes},

volume = {14},

issue = {7},

pages = {1386},

abstract = {The advent of next generation sequencing (NGS) has fostered a shift in basic analytic strategies of a gene expression analysis in diverse pathologies for the purposes of research, pharmacology, and personalized medicine. What was once highly focused research on individual signaling pathways or pathway members has, from the time of gene expression arrays, become a global analysis of gene expression that has aided in identifying novel pathway interactions, the discovery of new therapeutic targets, and the establishment of disease-associated profiles for assessing progression, stratification, or a therapeutic response. But there are significant caveats to this analysis that do not allow for the construction of the full picture. The lack of timely updates to publicly available databases and the "hit and miss" deposition of scientific data to these databases relegate a large amount of potentially important data to "garbage", begging the question, "how much are we really missing?" This brief perspective aims to highlight some of the limitations that RNA binding/modifying proteins and RNA processing impose on our current usage of NGS technologies as relating to cancer and how not fully appreciating the limitations of current NGS technology may negatively affect therapeutic strategies in the long run.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Yb_89,

title = {Alternative Splicing Changes Promoted by NOVA2 Upregulation in Endothelial Cells and Relevance for Gastric Cancer},

author = {{Di Matteo A} and Belloni E and Pradella D and Chiaravalli AM and Pini GM and Bugatti M and Alfieri R and Barzan C and Franganillo Tena E and Bione S and Terenzani E and Sessa F and Wyatt CDR and Vermi W and Ghigna C},

url = {https://pubmed.ncbi.nlm.nih.gov/37175811/},

doi = {10.3390/ijms24098102},

year  = {2023},

date = {2023-07-27},

urldate = {2023-07-27},

journal = {International journal of molecular sciences},

volume = {24},

issue = {9},

pages = {8102},

abstract = {Angiogenesis is crucial for cancer progression. While several anti-angiogenic drugs are in use for cancer treatment, their clinical benefits are unsatisfactory. Thus, a deeper understanding of the mechanisms sustaining cancer vessel growth is fundamental to identify novel biomarkers and therapeutic targets. Alternative splicing (AS) is an essential modifier of human proteome diversity. Nevertheless, AS contribution to tumor vasculature development is poorly known. The Neuro-Oncological Ventral Antigen 2 (NOVA2) is a critical AS regulator of angiogenesis and vascular development. NOVA2 is upregulated in tumor endothelial cells (ECs) of different cancers, thus representing a potential driver of tumor blood vessel aberrancies. Here, we identified novel AS transcripts generated upon NOVA2 upregulation in ECs, suggesting a pervasive role of NOVA2 in vascular biology. In addition, we report that NOVA2 is also upregulated in ECs of gastric cancer (GC), and its expression correlates with poor overall survival of GC patients. Finally, we found that the AS of the Rap Guanine Nucleotide Exchange Factor 6 (RapGEF6), a newly identified NOVA2 target, is altered in GC patients and associated with NOVA2 expression, tumor angiogenesis, and poor patient outcome. Our findings provide a better understanding of GC biology and suggest that AS might be exploited to identify novel biomarkers and therapeutics for anti-angiogenic GC treatments.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}