@article{%a1:%Y_133,

title = {5-Aza Exposure Improves Reprogramming Process Through Embryoid Body Formation in Human Gingival Stem Cells.},

author = {Diomede F and Zini N and Pizzicannella J and Merciaro I and Pizzicannella G and D'Orazio M and Piattelli A and Trubiani O},

url = {https://www.frontiersin.org/articles/10.3389/fgene.2018.00419/full},

doi = {10.3389/fgene.2018.00419},

year  = {2018},

date = {2018-02-21},

journal = {Frontiers in genetics},

volume = {9},

pages = {419},

abstract = {Embryoid bodies (EBs) are three-dimensional aggregates formed by pluripotent stem cells, including embryonic stem cells and induced pluripotent stem cells. They are used as an in vitro model to evaluate early extraembryonic tissue formation and differentiation process. In the adult organisms, cell differentiation is controlled and realized through the epigenetic regulation of gene expression, which consists of various mechanisms including DNA methylation. One demethylating agent is represented by 5-Azacytidine (5-Aza), considered able to induce epigenetic changes through gene derepression. Human gingival mesenchymal stem cells (hGMSCs), an easily accessible stem cells population, migrated from neural crest. They are particularly apt as an in vitro study model in regenerative medicine and in systemic diseases. The ability of 5-Aza treatment to induce hGMSCs toward a dedifferentiation stage and in particular versus EBs formation was investigated. For this purpose hGMSCs were treated for 48 h with 5-Aza (5 μM). After treatment, hGMSCs are organized as round 3D structures (EBs-hGMSCs). At light and transmission electron microscopy, the cells at the periphery of EBs-hGMSCs appear elongated, while ribbon-shaped cells and smaller cells with irregular shape surrounded by extracellular matrix were present in the center. By RT-PCR, EBs-hGMSCs expressed specific transcription markers related to the three germ layers as MAP-2, PAX-6 (ectoderm), MSX-1, Flk-1 (mesoderm), GATA-4, and GATA-6 (endoderm). Moreover, in EB-hGMSCs the overexpression of DNMT1 and ACH3 other than the down regulation of p21 was detectable. Immunofluorescence staining also showed a positivity for specific etodermal and mesodermal markers. In conclusion, 5-Aza was able to induce the direct conversion of adult hGMSCs into cells of three embryonic lineages: endoderm, ectoderm, and mesoderm, suggesting their possible application in autologous cell therapy for clinical organ repair.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_175,

title = {Evaluation of Lymphocyte Response to the Induced Oxidative Stress in a Cohort of Ageing Subjects, including Semisupercentenarians and Their Offspring.},

author = {Sizzano F and Collino S and Cominetti O and Monti D and Garagnani P and Ostan R and Pirazzini C and Bacalini MG and Mari D and Passarino G and Franceschi C and Palini A},

url = {https://www.hindawi.com/journals/mi/2018/7109312/},

doi = {10.1155/2018/7109312},

year  = {2018},

date = {2018-02-19},

journal = {Mediators of inflammation},

volume = {2018},

pages = {7109312},

abstract = {The production of reactive oxygen species (ROS) may promote immunosenescence if not counterbalanced by the antioxidant systems. Cell membranes, proteins, and nucleic acids become the target of ROS and progressively lose their structure and functions. This process could lead to an impairment of the immune response. However, little is known about the capability of the immune cells of elderly individuals to dynamically counteract the oxidative stress. Here, the response of the main lymphocyte subsets to the induced oxidative stress in semisupercentenarians (CENT), their offspring (OFF), elderly controls (CTRL), and young individuals (YO) was analyzed using flow cytometry. The results showed that the ratio of the ROS levels between the induced and noninduced (I/NI) oxidative stress conditions was higher in CTRL and OFF than in CENT and YO, in almost all T, B, and NK subsets. Moreover, the ratio of reduced glutathione levels between I/NI conditions was higher in OFF and CENT compared to the other groups in almost all the subsets. Finally, we observed significant correlations between the response to the induced oxidative stress and the degree of methylation in specific genes on the oxidative stress pathway. Globally, these data suggest that the capability to buffer dynamic changes in the oxidative environment could be a hallmark of longevity in humans.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_125,

title = {Collagen VI is required for the structural and functional integrity of the neuromuscular junction.},

author = {Cescon M and Gregorio I and Eiber N and Borgia D and Fusto A and Sabatelli P and Scorzeto M and Megighian A and Pegoraro E and Hashemolhosseini S and Bonaldo P},

url = {https://link.springer.com/article/10.1007%2Fs00401-018-1860-9},

doi = {10.1007/s00401-018-1860-9},

year  = {2018},

date = {2018-02-17},

journal = {Acta neuropathologica},

volume = {136},

number = {3},

pages = {483-499},

abstract = {The synaptic cleft of the neuromuscular junction (NMJ) consists of a highly specialized extracellular matrix (ECM) involved in synapse maturation, in the juxtaposition of pre- to post-synaptic areas, and in ensuring proper synaptic transmission. Key components of synaptic ECM, such as collagen IV, perlecan and biglycan, are binding partners of one of the most abundant ECM protein of skeletal muscle, collagen VI (ColVI), previously never linked to NMJ. Here, we demonstrate that ColVI is itself a component of this specialized ECM and that it is required for the structural and functional integrity of NMJs. In vivo, ColVI deficiency causes fragmentation of acetylcholine receptor (AChR) clusters, with abnormal expression of NMJ-enriched proteins and re-expression of fetal AChRγ subunit, both in Col6a1 null mice and in patients affected by Ullrich congenital muscular dystrophy (UCMD), the most severe form of ColVI-related myopathies. Ex vivo muscle preparations from ColVI null mice revealed altered neuromuscular transmission, with electrophysiological defects and decreased safety factor (i.e., the excess current generated in response to a nerve impulse over that required to reach the action potential threshold). Moreover, in vitro studies in differentiated C2C12 myotubes showed the ability of ColVI to induce AChR clustering and synaptic gene expression. These findings reveal a novel role for ColVI at the NMJ and point to the involvement of NMJ defects in the etiopathology of ColVI-related myopathies.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_162,

title = {Efficient optimization of pyrazolo[3,4-d]pyrimidines derivatives as c-Src kinase inhibitors in neuroblastoma treatment.},

author = {Molinari A and Fallacara AL and Di Maria S and Zamperini C and Poggialini F and Musumeci F and Schenone S and Angelucci A and Colapietro A and Crespan E and Kissova M and Maga G and Botta M},

url = {https://www.sciencedirect.com/science/article/pii/S0960894X18307558?via%3Dihub},

doi = {10.1016/j.bmcl.2018.09.024},

year  = {2018},

date = {2018-02-17},

journal = {Bioorganic & medicinal chemistry letters},

volume = {28},

number = {21},

pages = {3454-3457},

abstract = {The proto-oncogene c-Src is a non-receptor tyrosine kinase which is involved in the regulation of many cellular processes, such as differentiation, adhesion and survival. c-Src hyperactivation has been detected in many tumors, including neuroblastoma (NB), one of the major causes of death from neoplasia in infancy. We already reported a large family of pyrazolo[3,4-d]pyrimidines active as c-Src inhibitors. Interestingly, some of these derivatives resulted also active on SH-SY5Y NB cell line. Herein, starting from our previous Free Energy Perturbation/Monte Carlo calculations, we report an optimization study which led to the identification of a new series of derivatives endowed with nanomolar Ki values against c-Src, interesting antiproliferative activity on SH-SY5Y cells and a suitable ADME profile.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_244,

title = {An Innovative Cell Microincubator for Drug Discovery Based on 3D Silicon Structures},

author = {Aredia F and Carpignano F and Surdo S and Barillaro G and Mazzini G and Scovassi AI and Merlo S},

url = {https://www.hindawi.com/journals/jnm/2016/8236539/},

doi = {10.1155/2016/8236539},

year  = {2018},

date = {2018-02-16},

journal = {Journa of Nanomaterials},

volume = {2016},

pages = {8236539},

abstract = {Recently, we applied three-dimensional (3D) silicon microstructures (SMSs), consisting of arrays of ?3 "m-thick silicon walls separated by 50 "m-deep, ?5 "m-wide gaps, as microincubators suitable for monitoring the biomechanical properties of tumor cells in culture.The same structures were here employed to investigate the in vitro behavior of tumor cells driven to apoptosis by a chemotherapeutic compound. HT1080 human fibrosarcoma cells were grown on silicon dice incorporating the 3D-SMSs, treated with the proapoptotic drug Bleomycin (200 "g/mL for 24 h, 48 h, and 72 h), and fixed and stained for fluorescence microscopy analyses. Results of our investigation demonstrated that HT1080 cells exhibited a great ability to colonize the grooves, entering the narrow, deep gaps of the 3D-SMS. We also observed that cells grown on 3D-SMS, when treated with the DNA damaging agent Bleomycin under conditions leading to apoptosis, tended to shrink, reducing their volume and mimicking the normal behavior of apoptotic cells, and to leave the gaps. Visual inspection performed bymeans of fluorescencemicroscopy allowed us to demonstrate that cells grown on 3D-SMS exhibited the morphological alterations typical of apoptosis. In view of future applications of the 3DSMS as the core element of a lab-on-a-chip suitable for screening the effect of new molecules potentially able to kill tumor cells, we also performed label-free detection of a cell adherent to the vertical siliconwall, inside the gap of 3D-SMS, by exploitingOptical Low Coherence Reflectometry using infrared, low power radiation.This kind of lab-on-a-chip combined with label-free cell detection may become a new tool for increasing automation in the drug discovery area.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_110,

title = {Exosome-like nanovesicles isolated from Citrus limon L. exert antioxidative effect.},

author = {Baldini N and Torreggiani E and Roncuzzi L and Perut F and Zini N and Avnet S},

url = {http://www.eurekaselect.com/166345/article},

doi = {10.2174/1389201019666181017115755},

year  = {2018},

date = {2018-02-16},

journal = {Current pharmaceutical biotechnology},

volume = {19},

number = {11},

pages = {877-885},

abstract = {Background: Exosome-like nanovesicles are biological nanostructures mediating cell-tocell communication and capable to load selected cargos also in the interaction among different species. Objective: We aimed to explore the content of exosome-like nanovesicles derived from Citrus limon L. and to analyze the effects of their uptake on human cells. Method: We isolated exosome-like nanovesicles from Citrus limon L. juice (EXO-CLs) by differential centrifugation. EXO-CLs were analyzed for short RNA content by advanced sequencing technologies, and for ascorbic acid (vitamin C) and citrate content by enzymatic assays. EXO-CLs anti-oxidant and pro-differentiative potential was evaluated in vitro on mesenchymal stromal cells (MSC), a common tool for regenerative strategies for several human tissues. Results: We showed that EXO-CLs carry detectable amounts of citrate and vitamin C and, although it was not possible to identify specific miRNAs, we detected short RNA sequences (20-30 bp) with unknown functions and with different distribution size in respect to whole Citrus limon L. juice. In vitro, EXO-CLs were uptaken by MSC and had a significant protective effect against oxidative stress. Furthermore, regarding the potential benefit for human bone health, we found that EXO-CLs modulate MSC differentiation versus the osteogenic lineage. Conclusion: We demonstrated that incubation with EXO-CLs exert antioxidant activity in human cells. This is most likely due to the direct delivery and uptake of micronutrients by human cells that are well preserved inside the nanovesicle membrane, including the unstable vitamin C. Based on our results, we speculate that fruit-derived nanovesicles have the potential to mediate interspecies influence after food intake.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_118,

title = {Cardiolaminopathies from bench to bedside: challenges in clinical decision-making with focus on arrhythmia-related outcomes. },

author = {Boriani G and Biagini E and Ziacchi M and Malavasi VL and Vitolo M and Talarico M and Mauro E and Gorlato G and Lattanzi G},

url = {https://www.tandfonline.com/doi/full/10.1080/19491034.2018.1506680},

doi = {10.1080/19491034.2018.1506680},

year  = {2018},

date = {2018-02-16},

journal = {Nucleus},

volume = {9},

number = {1},

pages = {442-459},

abstract = {Lamin A/C gene mutations can be associated with cardiac diseases, usually referred to as "cardiolaminopathies" characterized by arrhythmic disorders and/or left ventricular or biventricular dysfunction up to an overt picture of heart failure. The phenotypic cardiac manifestations of laminopathies are frequently mixed in complex clinical patterns and specifically may include bradyarrhythmias (sinus node disease or atrioventricular blocks), atrial arrhythmias (atrial fibrillation, atrial flutter, atrial standstill), ventricular tachyarrhythmias and heart failure of variable degrees of severity. Family history, physical examination, laboratory findings (specifically serum creatine phosphokinase values) and ECG findings are often important "red flags" in diagnosing a "cardiolaminopathy". Sudden arrhythmic death, thromboembolic events or stroke and severe heart failure requiring heart transplantation are the most dramatic complications of the evolution of cardiolaminopathies and appropriate risk stratification is clinically needed combined with clinical follow-up. Treatment with cardiac electrical implantable devices is indicated in case of bradyarrhythmias (implant of a device with pacemaker functions), risk of life-threatening ventricular tachyarrhythmias (implant of an ICD) or in case of heart failure with wide QRS interval (implant of a device for cardiac resynchronization). New technologies introduced in the last 5 years can help physicians to reduce device-related complications, thanks to the extension of device longevity and availability of leadless pacemakers or defibrillators, to be implanted in appropriately selected patients. An improved knowledge of the complex pathophysiological pathways involved in cardiolaminopathies and in the determinants of their progression to more severe forms will help to improve clinical management and to better target pharmacological and non-pharmacological treatments.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_127,

title = {Serum and Hepatic Autofluorescence as a Real-Time Diagnostic Tool for Early Cholestasis Assessment.},

author = {Croce AC and Bottiroli G and Di Pasqua LG and Berardo C and Siciliano V and Rizzo V and Vairetti M and Ferrigno A},

url = {https://www.mdpi.com/1422-0067/19/9/2634},

doi = {10.3390/ijms19092634},

year  = {2018},

date = {2018-02-16},

journal = {International journal of molecular sciences.},

volume = {19},

number = {9},

pages = {pii: E2634},

abstract = {While it is well established that various factors can impair the production and flow of bile and lead to cholestatic disease in hepatic and extrahepatic sites, an enhanced assessment of the biomarkers of the underlying pathophysiological mechanisms is still needed to improve early diagnosis and therapeutic strategies. Hence, we investigated fluorescing endogenous biomolecules as possible intrinsic biomarkers of molecular and cellular changes in cholestasis. Spectroscopic autofluorescence (AF) analysis was performed using a fiber optic probe (366 nm excitation), under living conditions and in serum, on the livers of male Wistar rats submitted to bile duct ligation (BDL, 24, 48, and 72 h). Biomarkers of liver injury were assayed biochemically. In the serum, AF analysis distinctly detected increased bilirubin at 24 h BDL. A continuous, significant increase in red-fluorescing porphyrin derivatives indicated the subversion of heme metabolism, consistent with an almost twofold increase in the serum iron at 72 h BDL. In the liver, changes in the AF of NAD(P)H and flavins, as well as lipopigments, indicated the impairment of mitochondrial functionality, oxidative stress, and the accumulation of oxidative products. A serum/hepatic AF profile can be thus proposed as a supportive diagnostic tool for the in situ, real-time study of bio-metabolic alterations in bile duct ligation (BDL) in experimental hepatology, with the potential to eventually translate to clinical diagnosis.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_134,

title = {CREBBP and p300 lysine acetyl transferases in the DNA damage response.},

author = {Dutto I and Scalera C and Prosperi E},

url = {https://link.springer.com/article/10.1007%2Fs00018-017-2717-4},

doi = {10.1007/s00018-017-2717-4},

year  = {2018},

date = {2018-02-16},

journal = {Cellular and molecular life sciences: CMLS},

volume = {75},

number = {8},

pages = {1325-1338},

abstract = {The CREB-binding protein (CREBBP, or in short CBP) and p300 are lysine (K) acetyl transferases (KAT) belonging to the KAT3 family of proteins known to modify histones, as well as non-histone proteins, thereby regulating chromatin accessibility and transcription. Previous studies have indicated a tumor suppressor function for these enzymes. Recently, they have been found to acetylate key factors involved in DNA replication, and in different DNA repair processes, such as base excision repair, nucleotide excision repair, and non-homologous end joining. The growing list of CBP/p300 substrates now includes factors involved in DNA damage signaling, and in other pathways of the DNA damage response (DDR). This review will focus on the role of CBP and p300 in the acetylation of DDR proteins, and will discuss how this post-translational modification influences their functions at different levels, including catalytic activity, DNA binding, nuclear localization, and protein turnover. In addition, we will exemplify how these functions may be necessary to efficiently coordinate the spatio-temporal response to DNA damage. CBP and p300 may contribute to genome stability by fine-tuning the functions of DNA damage signaling and DNA repair factors, thereby expanding their role as tumor suppressors.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_152,

title = {Genome Analyses of >200,000 Individuals Identify 58 Loci for Chronic Inflammation and Highlight Pathways that Link Inflammation and Complex Disorders.},

author = {Ligthart S and Vaez A and Vosa U and et al and Biino G and et al



},

url = {https://www.sciencedirect.com/science/article/pii/S0002929718303203?via%3Dihub},

doi = {10.1016/j.ajhg.2018.09.009},

year  = {2018},

date = {2018-02-16},

journal = {Annals of Human Genetics},

volume = {103},

number = {5},

pages = {691-706},

abstract = {C-reactive protein (CRP) is a sensitive biomarker of chronic low-grade inflammation and is associated with multiple complex diseases. The genetic determinants of chronic inflammation remain largely unknown, and the causal role of CRP in several clinical outcomes is debated. We performed two genome-wide association studies (GWASs), on HapMap and 1000 Genomes imputed data, of circulating amounts of CRP by using data from 88 studies comprising 204,402 European individuals. Additionally, we performed in silico functional analyses and Mendelian randomization analyses with several clinical outcomes. The GWAS meta-analyses of CRP revealed 58 distinct genetic loci (p < 5 × 10-8). After adjustment for body mass index in the regression analysis, the associations at all except three loci remained. The lead variants at the distinct loci explained up to 7.0% of the variance in circulating amounts of CRP. We identified 66 gene sets that were organized in two substantially correlated clusters, one mainly composed of immune pathways and the other characterized by metabolic pathways in the liver. Mendelian randomization analyses revealed a causal protective effect of CRP on schizophrenia and a risk-increasing effect on bipolar disorder. Our findings provide further insights into the biology of inflammation and could lead to interventions for treating inflammation and its clinical consequences.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_323,

title = {Cells with stemness features are generated from in vitro transformed human fibroblasts.},

author = {Bono B and Ostano P and Peritore M and Gregnanin I and Belgiovine C and Liguori M and Allavena P and Chiorino G and Chiodi I and Mondello C},

url = {https://www.nature.com/articles/s41598-018-32197-5},

doi = {10.1038/s41598-018-32197-5},

year  = {2018},

date = {2018-02-15},

journal = {Scientific Reports},

volume = {8},

number = {1},

pages = {13838},

abstract = {Cancer stem cells (CSCs) have been involved in the maintenance, progression and relapse of several tumors, but their origin is still elusive. Here, in vitro transformed human fibroblasts (cen3tel cells) and the tumorsphere assay were used to search for and possibly characterize CSCs in transformed somatic cells. Cen3tel cells formed spheres showing self-renewal capacity and Sox2 overexpression, suggesting that they contained a subset of cells with CSC-like features. Sphere cells displayed deregulation of a c-MYC/miR-34a circuitry, likely associated with cell protection from apoptosis. Gene expression profiles of sphere cells revealed an extensive transcriptional reprogramming. Genes up-regulated in tumorspheres identified processes related to tumorigenesis and stemness, as cholesterol biosynthesis, apoptosis suppression, interferon and cytokine mediated signalling pathways. Sphere cells engrafted into NSG mice more rapidly than adherent cells, but both cell populations were tumorigenic. These results indicate that, during transformation, human somatic cells can acquire CSC properties, confirming the high plasticity of tumor cells. However, CSC-like cells are not the only tumorigenic population in transformed cells, indicating that the CSC phenotype and tumorigenicity can be uncoupled.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_126,

title = {Ozone Treatment of Grapes During Withering for Amarone Wine: A Multimodal Imaging and Spectroscopic Analysis.},

author = {Cisterna B and Boschi F and Croce AC and Podda R and Zanzoni S and Degl'Innocenti D and Bernardi P and Costanzo M and Marzola P and Covi V and Tabaracci G and Malatesta M},

url = {https://www.cambridge.org/core/journals/microscopy-and-microanalysis/article/ozone-treatment-of-grapes-during-withering-for-amarone-wine-a-multimodal-imaging-and-spectroscopic-analysis/BB236A32C1A9BBA6619E001BB025BEF1},

doi = {10.1017/S1431927618015209},

year  = {2018},

date = {2018-02-15},

journal = {Microscopy and microanalysis},

volume = {24},

number = {5},

pages = {564-573},

abstract = {The production of Amarone wine is governed by a disciplinary guideline to preserve its typical features; however, postharvest infections by the fungus Botrytis cinerea (B. cinerea) not only represent a phytosanitary problem but also cause a significant loss of product. In this study, we tested a treatment with mild ozoniztion on grapes for Amarone wine production during withering in the fruttaio (the environment imposed by the disciplinary guideline) and evaluated the impact on berry features by a multimodal imaging approach. The results indicate that short and repeated treatments with low O3 concentrations speed up the naturally occurring berry withering, probably inducing a reorganization of the epicuticular wax layer, and inhibit the development of B. cinerea, blocking the fungus in an intermediate vegetative stage. This pilot study will pave the way to long-term research on Amarone wine obtained from O3-treated grapes.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_142,

title = {A Novel Role for the Interleukin-1 Receptor Axis in Resistance to Anti-EGFR Therapy.},

author = {Gelfo V and Mazzeschi M and Grilli G and Lindzen M and Santi S and D'Uva G and Gyorffy B and Ardizzoni A and Yarden Y and Lauriola M},

url = {https://www.mdpi.com/2072-6694/10/10/355 },

doi = {10.3390/cancers10100355.},

year  = {2018},

date = {2018-02-15},

journal = {Cancers},

volume = {10},

number = {10},

pages = {pii: E365},

abstract = {Cetuximab (CTX) is a monoclonal antibody targeting the epidermal growth factor receptor (EGFR), commonly used to treat patients with metastatic colorectal cancer (mCRC). Unfortunately, objective remissions occur only in a minority of patients and are of short duration, with a population of cells surviving the treatment and eventually enabling CTX resistance. Our previous study on CRC xenopatients associated poor response to CTX with increased abundance of a set of pro-inflammatory cytokines, including the interleukins IL-1A, IL-1B and IL-8. Stemming from these observations, our current work aimed to assess the role of IL-1 pathway activity in CTX resistance. We employed a recombinant decoy TRAP IL-1, a soluble protein combining the human immunoglobulin Fc portion linked to the extracellular region of the IL-1-receptor (IL-1R1), able to sequester IL-1 directly from the medium. We generated stable clones expressing and secreting a functional TRAP IL-1 into the culture medium. Our results show that IL-1R1 inhibition leads to a decreased cell proliferation and a dampened MAPK and AKT axes. Moreover, CRC patients not responding to CTX blockage displayed higher levels of IL-1R1 than responsive subjects, and abundant IL-1R1 is predictive of survival in patient datasets specifically for the consensus molecular subtype 1 (CMS1). We conclude that IL-1R1 abundance may represent a therapeutic marker for patients who become refractory to monoclonal antibody therapy, while inhibition of IL-1R1 by TRAP IL-1 may offer a novel therapeutic strategy.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_164,

title = {Diversification of the muscle proteome through alternative splicing.},

author = {Nakka K and Ghigna C and Gabellini D and Dilworth FJ},

url = {https://skeletalmusclejournal.biomedcentral.com/articles/10.1186/s13395-018-0152-3},

doi = {Skeletal Muscle},

year  = {2018},

date = {2018-02-15},

urldate = {2018-02-15},

journal = {Skeletal Muscle},

volume = {8},

number = {1},

pages = {8},

abstract = {Skeletal Muscle},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_168,

title = {A damaged DNA binding protein 2 mutation disrupting interaction with proliferating-cell nuclear antigen affects DNA repair and confers proliferation advantage.},

author = {Perucca P and Mocchi R and Guardamagna I and Bassi E and Sommatis S and Nardo T and Prosperi E and Stivala LA and Cazzalini O},

url = {https://www.sciencedirect.com/science/article/pii/S0167488918300569?via%3Dihub},

doi = {10.1016/j.bbamcr.2018.03.012},

year  = {2018},

date = {2018-02-15},

journal = {Biochimica et Biophysica Acta (BBA) - Molecular Cell Research},

volume = {1865},

number = {6},

pages = {898-907},

abstract = {n mammalian cells, Nucleotide Excision Repair (NER) plays a role in removing DNA damage induced by UV radiation. In Global Genome-NER subpathway, DDB2 protein forms a complex with DDB1 (UV-DDB), recognizing photolesions. During DNA repair, DDB2 interacts directly with PCNA through a conserved region in N-terminal tail and this interaction is important for DDB2 degradation. In this work, we sought to investigate the role of DDB2-PCNA association in DNA repair and cell proliferation after UV-induced DNA damage. To this end, stable clones expressing DDB2Wt and DDB2PCNA- were used. We have found that cells expressing a mutant DDB2 show inefficient photolesions removal, and a concomitant lack of binding to damaged DNA in vitro. Unexpected cellular behaviour after DNA damage, such as UV-resistance, increased cell growth and motility were found in DDB2PCNA- stable cell clones, in which the most significant defects in cell cycle checkpoint were observed, suggesting a role in the new cellular phenotype. Based on these findings, we propose that DDB2-PCNA interaction may contribute to a correct DNA damage response for maintaining genome integrity.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_169,

title = {Electrochemically Synthesized Silver Nanoparticles Are Active Against Planktonic and Biofilm Cells of Pseudomonas aeruginosa and Other Cystic Fibrosis-Associated Bacterial Pathogens.},

author = {Pompilio A and Geminiani C and Bosco D and Rana R and Aceto A and Bucciarelli T and Scotti L and Di Bonaventura G},

url = {https://www.frontiersin.org/articles/10.3389/fmicb.2018.01349/full},

doi = {10.3389/fmicb.2018.01349},

year  = {2018},

date = {2018-02-15},

journal = {Frontiers in microbiology},

volume = {9},

pages = {1349},

abstract = {1349},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_182,

title = {BK channel overexpression on plasma membrane of fibroblasts from Hutchinson-Gilford progeria syndrome.},

author = {Zironi I and Gavoci E and Lattanzi G and Virelli A and Amorini F and Remondini D and Castellani G},

url = {https://www.aging-us.com/article/101621/text},

doi = {10.18632/aging.101621},

year  = {2018},

date = {2018-02-15},

journal = {Aging (Albany, NY)},

volume = {10},

number = {11},

pages = {3148-3160},

abstract = {Hutchinson-Gilford progeria syndrome (HGPS) is an extremely rare genetic disorder wherein symptoms resembling aspects of aging are manifested at a very early age. It is a genetic condition that occurs due to a de novo mutation in the LMNA gene encoding for the nuclear structural protein lamin A. The lamin family of proteins are thought to be involved in nuclear stability, chromatin structure and gene expression and this leads to heavy effects on the regulation and functionality of the cell machinery. The functional role of the large-conductance calcium-activated potassium channels (BKCa) is still unclear, but has been recently described a strong relationship with their membrane expression, progerin nuclear levels and the ageing process. In this study, we found that: i) the outward potassium membrane current amplitude and the fluorescence intensity of the BKCa channel probe showed higher values in human dermal fibroblast obtained from patients affected by HGPS if compared to that from healthy young subjects; ii) this result appears to correlate with a basic cellular activity such as the replicative boost. We suggest that studying the HGPS also from the electrophysiological point of view might reveal new clues about the normal process of aging.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_112,

title = {Dual inhibition of PI3K/mTOR signaling in chemoresistant AML primary cells.},

author = {Bertacchini J and Frasson C and Chiarini F and D'Avella D and Accordi B and Anselmi L and Barozzi P and Foghieri F and Luppi M and Martelli AM and Basso G and Najmaldin S and Khosravi A and Rahim F and Marmiroli S},

url = {10.1016/j.jbior.2018.03.001},

doi = {10.1016/j.jbior.2018.03.001},

year  = {2018},

date = {2018-02-14},

journal = {Advances in biological regulation},

volume = {68},

number = {2},

pages = {9},

abstract = {A main cause of treatment failure for AML patients is resistance to chemotherapy. Survival of AML cells may depend on mechanisms that elude conventional drugs action and/or on the presence of leukemia initiating cells at diagnosis, and their persistence after therapy. MDR1 gene is an ATP-dependent drug efflux pump known to be a risk factor for the emergence of resistance, when combined to unstable cytogenetic profile of AML patients. In the present study, we analyzed the sensitivity to conventional chemotherapeutic drugs of 26 samples of primary blasts collected from AML patients at diagnosis. Detection of cell viability and apoptosis allowed to identify two group of samples, one resistant and one sensitive to in vitro treatment. The cells were then analyzed for the presence and the activity of P-glycoprotein. A comparative analysis showed that resistant samples exhibited a high level of MDR1 mRNA as well as of P-glycoprotein content and activity. Moreover, they also displayed high PI3K signaling. Therefore, we checked whether the association with signaling inhibitors might resensitize resistant samples to chemo-drugs. The combination showed a very potent cytotoxic effect, possibly through down modulation of MDR1, which was maintained also when primary blasts were co-cultured with human stromal cells. Remarkably, dual PI3K/mTOR inactivation was cytotoxic also to leukemia initiating cells. All together, our findings indicate that signaling activation profiling associated to gene expression can be very useful to stratify patients and improve therapy.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_116,

title = {Ripples on the surface. Surnames and genes in Sicily and Southern Italy.},

author = {Boattini A and Sarno S and Fiorani O and Lisa A and Luiselli D and Pettener D},

url = {http://www.tandfonline.com/doi/abs/10.1080/03014460.2017.1411525?journalCode=iahb20},

doi = {10.1080/03014460.2017.1411525},

year  = {2018},

date = {2018-02-14},

journal = {Annals of Human Biology},

volume = {45},

number = {1},

pages = {57-65},

abstract = {Southern Italy and Sicily played a key role in the peopling history of the Mediterranean. While genetic research showed the remarkable homogeneity of these regions, surname-based studies instead suggested low population mobility, hence potential structuring. AIM: In order to better understand these different patterns, this study (1) thoroughly analysed the surname structure of Sicily and Southern Italy and (2) tested its relationships with a wide set of molecular markers. SUBJECTS AND METHODS: Surname data were collected from 1213 municipalities and compared to uniparental and autosomal genetic markers typed in about 300 individuals from 8-10 populations. Surname analyses were performed using different multivariate methods, while comparisons with genetic data relied on correlation tests. RESULTS: Surnames were clearly structured according to regional geographic patterns, which likely emerged because of recent isolation-by-distance-like population dynamics. In general, genetic markers, hinting at a pervasive homogeneity, did not correlate with surname distribution. However, long autosomal haplotypes (>5 cM) that compared to genotypic (SNPs) data identify more "recent" relatedness, showing a clear association with surname patterns. CONCLUSION: The apparent contradiction between surname structure and genetic homogeneity was resolved by figuring surnames as recent "ripples" deposited on a vast and ancient homogeneous genetic "surface".},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_117,

title = {Cells Escape an Operational Mitotic Checkpoint through a Stochastic Process.},

author = {Bonaiuti P and Chiroli E and Gross F and Corno A and Vernieri C and Stefl M and Cosentino Lagomarsino M and Knop M and Ciliberto A},

url = {https://www.sciencedirect.com/science/article/pii/S0960982217315130?via%3Dihub},

doi = {10.1016/j.cub.2017.11.031},

year  = {2018},

date = {2018-02-14},

journal = {Current Biology},

volume = {28},

number = {1},

pages = {28-37},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_119,

title = {Dormant origins and fork protection mechanisms rescue sister forks arrested by transcription.},

author = {Brambati A and Zardoni L and Achar YJ and Piccini D and Galanti L and Colosio A and Foiani M and Liberi G},

url = {https://academic.oup.com/nar/advance-article/doi/10.1093/nar/gkx945/4559489},

doi = {doi.org/10.1093/nar/gkx945},

year  = {2018},

date = {2018-02-14},

journal = {Nucleic Acids Research},

volume = {46},

number = {3},

pages = {12271239},

abstract = {The yeast RNA/DNA helicase Sen1, Senataxin in human, preserves the integrity of replication forks encountering transcription by removing RNA-DNA hybrids. Here we show that, in sen1 mutants, when a replication fork clashes head-on with transcription is arrested and, as a consequence, the progression of the sister fork moving in the opposite direction within the same replicon is also impaired. Therefore, sister forks remain coupled when one of the two forks is arrested by transcription, a fate different from that experienced by forks encountering Double Strand Breaks. We also show that dormant origins of replication are activated to ensure DNA synthesis in the proximity to the forks arrested by transcription. Dormant origin firing is not inhibited by the replication checkpoint, rather dormant origins are fired if they cannot be timely inactivated by passive replication. In sen1 mutants, the Mre11 and Mrc1-Ctf4 complexes protect the forks arrested by transcription from processing mediated by the Exo1 nuclease. Thus, a harmless head-on replication-transcription clash resolution requires the fine-tuning of origin firing and coordination among Sen1, Exo1, Mre11 and Mrc1-Ctf4 complexes.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_154,

title = {Cell cycle and apoptosis regulator 2 at the interface between DNA damage response and cell physiology},

author = {Magni M and Buscemi G and Zannini L},

url = {https://www.sciencedirect.com/science/article/pii/S1383574218300073?via%3Dihub},

doi = {10.1016/j.mrrev.2018.03.004},

year  = {2018},

date = {2018-02-14},

journal = {Mutation research - Reviews in Mutation Research},

volume = {776},

pages = {1-9},

abstract = {Cell cycle and apoptosis regulator 2 (CCAR2 or DBC1) is a human protein recently emerged as a novel and important player of the DNA damage response (DDR). Indeed, upon genotoxic stress, CCAR2, phosphorylated by the apical DDR kinases ATM and ATR, increases its binding to the NAD+-dependent histone deacetylase SIRT1 and inhibits SIRT1 activity. This event promotes the acetylation and activation of p53, a SIRT1 target, and the subsequent induction of p53 dependent apoptosis. In addition, CCAR2 influences DNA repair pathway choice and promotes the chromatin relaxation necessary for the repair of heterochromatic DNA lesions. However, besides DDR, CCAR2 is involved in several other cellular functions. Indeed, through the interaction with transcription factors, nuclear receptors, epigenetic modifiers and RNA polymerase II, CCAR2 regulates transcription and transcript elongation. Moreover, promoting Rev-erbα protein stability and repressing BMAL1 and CLOCK expression, it was reported to modulate the circadian rhythm. Through SIRT1 inhibition, CCAR2 is also involved in metabolism control and, suppressing RelB and p65 activities in the NFkB pathway, it restricts B cell proliferation and immunoglobulin production. Notably, CCAR2 expression is deregulated in several tumors and, compared to the non-neoplastic counterpart, it may be up- or down-regulated. Since its up-regulation in cancer patients is usually associated with poor prognosis and its depletion reduces cancer cell growth in vitro, CCAR2 was suggested to act as a tumor promoter. However, there is also evidence that CCAR2 functions as a tumor suppressor and therefore its role in cancer formation and progression is still unclear. In this review we discuss CCAR2 functions in the DDR and its multiple biological activities in unstressed cells.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_159,

title = {Altered modulation of lamin A/C-HDAC2 interaction and p21 expression during oxidative stress response in HGPS.},

author = {Mattioli E and Andrenacci D and Garofalo C and Prencipe S and Scotlandi K and Remondini D and Gentilini D and {Di Blasio AM} and Valente S and Scarano E and Cicchilitti L and Piaggio G and Mai A and Lattanzi G},

url = {https://onlinelibrary.wiley.com/doi/abs/10.1111/acel.12824},

doi = {10.1111/acel.12824},

year  = {2018},

date = {2018-02-14},

journal = {Aging cell},

volume = {17},

number = {5},

pages = {e1282},

abstract = {Defects in stress response are main determinants of cellular senescence and organism aging. In fibroblasts from patients affected by Hutchinson-Gilford progeria, a severe LMNA-linked syndrome associated with bone resorption, cardiovascular disorders, and premature aging, we found altered modulation of CDKN1A, encoding p21, upon oxidative stress induction, and accumulation of senescence markers during stress recovery. In this context, we unraveled a dynamic interaction of lamin A/C with HDAC2, an histone deacetylase that regulates CDKN1A expression. In control skin fibroblasts, lamin A/C is part of a protein complex including HDAC2 and its histone substrates; protein interaction is reduced at the onset of DNA damage response and recovered after completion of DNA repair. This interplay parallels modulation of p21 expression and global histone acetylation, and it is disrupted by LMNAmutations leading to progeroid phenotypes. In fact, HGPS cells show impaired lamin A/C-HDAC2 interplay and accumulation of p21 upon stress recovery. Collectively, these results link altered physical interaction between lamin A/C and HDAC2 to cellular and organism aging. The lamin A/C-HDAC2 complex may be a novel therapeutic target to slow down progression of progeria symptoms.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_171,

title = {Age-Related Epigenetic Derangement upon Reprogramming and Differentiation of Cells from the Elderly.},

author = {Ravaioli F and Bacalini MG and Franceschi C and Garagnani P},

url = {https://www.mdpi.com/2073-4425/9/1/39},

doi = {10.3390/genes9010039},

year  = {2018},

date = {2018-02-14},

urldate = {2018-02-14},

journal = {Genes},

volume = {9},

number = {1},

pages = {pii: E39},

abstract = {Aging is a complex multi-layered phenomenon. The study of aging in humans is based on the use of biological material from hard-to-gather tissues and highly specific cohorts. The introduction of cell reprogramming techniques posed promising features for medical practice and basic research. Recently, a growing number of studies have been describing the generation of induced pluripotent stem cells (iPSCs) from old or centenarian biologic material. Nonetheless, Reprogramming techniques determine a profound remodelling on cell epigenetic architecture whose extent is still largely debated. Given that cell epigenetic profile changes with age, the study of cell-fate manipulation approaches on cells deriving from old donors or centenarians may provide new insights not only on regenerative features and physiology of these cells, but also on reprogramming-associated and age-related epigenetic derangement.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_111,

title = {Elevated TGF beta2 serum levels in Emery-Dreifuss muscular dystrophy: implications for myocyte and tenocyte differentiation and fibrogenic processes.},

author = {Bernasconi P and Carboni N and Ricci G and Siciliano G and Politano L and Maggi L and Mongini T and Vercelli L and Rodolico C and Biagini E and Boriani G and Ruggiero L and Santoro L and Schena E and Prencipe S and Evangelisti C and Pegoraro E and Morandi L and Columbaro M and Lanzuolo C and Sabatelli P and Cavalcante P and Cappelletti C and Bonne G and Muchir A and Lattanzi G},

url = {https://www.tandfonline.com/doi/abs/10.1080/19491034.2018.1467722},

doi = {10.1080/19491034.2018.1467722},

year  = {2018},

date = {2018-02-13},

journal = {Nucleus},

volume = {25},

number = {1},

pages = {24},

abstract = {Among rare diseases caused by mutations in LMNA gene, Emery-Dreifuss Muscular Dystrophy type 2 and Limb-Girdle muscular Dystrophy 1B are characterized by muscle weakness and wasting, joint contractures, cardiomyopathy with conduction system disorders. Circulating biomarkers for these pathologies have not been identified. Here, we analyzed the secretome of a cohort of patients affected by these muscular laminopathies in the attempt to identify a common signature. Multiplex cytokine assay showed that transforming growth factor beta 2 (TGF beta2) and interleukin 17 serum levels are consistently elevated in the vast majority of examined patients, while interleukin 6 and basic fibroblast growth factor are altered in subgroups of patients. Levels of TGF beta2 are also increased in fibroblast and myoblast cultures established from patient biopsies as well as in serum from mice bearing the H222P Lmna mutation causing Emery-Dreifuss muscular dystrophy in humans. Both patient serum and fibroblast conditioned media activated a TGF beta2-dependent fibrogenic program in normal human myoblasts and tenocytes and inhibited myoblast differentiation. Consistent with these results, a TGF beta2 neutralizing antibody avoided fibrogenic marker activation and myogenesis impairment. Cell intrinsic TGF beta2-dependent mechanisms were also determined in laminopathic cells, where TGF beta2 activated AKT/mTOR phosphorylation. These data show that TGF beta2 contributes to the pathogenesis of Emery-Dreifuss Muscular Dystrophy type 2 and Limb-Girdle muscular Dystrophy 1B and can be considered a potential biomarker of those diseases. Further, the evidence of TGF beta2 pathogenetic effects in tenocytes provides the first mechanistic insight into occurrence of joint contractures in muscular laminopathies},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_128,

title = {Autofluorescence based optical biopsy: an effective diagnostic tool in hepatology.},

author = {Croce AC and Ferrigno A and Bottiroli G and Vairetti M},

url = {https://onlinelibrary.wiley.com/doi/abs/10.1111/liv.13753},

doi = {10.1111/liv.13753},

year  = {2018},

date = {2018-02-07},

journal = {Liver International},

volume = {38},

number = {7},

pages = {1160-1174},

abstract = {Autofluorescence emission of liver tissue depends on the presence of endogenous biomolecules able to fluoresce under suitable light excitation. Overall autofluorescence emission contains much information of diagnostic value, because it is the sum of individual autofluorescence contributions from fluorophores involved in metabolism, for example NAD(P)H, flavins, lipofuscins, retinoids, porphyrins, bilirubin and lipids, or in structural architecture, for example fibrous proteins, in close relationship with normal, altered or diseased conditions of the liver. Since the 1950s, hepatocytes and liver have been historical models to study NAD(P)H and flavins as in situ, real time autofluorescence biomarkers of energy metabolism and redox state. Later investigations designed to monitor organ responses to ischemia/reperfusion, were able to predict the risk of dysfunction in surgery and transplantation, or support the development of procedures to ameliorate the liver outcome. Subsequently, fluorescent fatty acids, lipofuscin‐like lipopigments and collagen were characterized as optical biomarkers of liver steatosis, oxidative stress damage, fibrosis and disease progression. Currently, serum AF is being investigated to improve non invasive optical diagnosis of liver disease. Validation of endogenous fluorophores and in situ discrimination of cancerous from non‐cancerous tissue belong to the few studies on liver in human subjects. These reports, along with other optical techniques and the huge work performed on animal models suggest many optically based applications in hepatology. Optical diagnosis is currently offering beneficial outcomes in clinical fields ranging from the respiratory and gastrointestinal tracts, to dermatology and ophthalmology. Accordingly, this review aims to promote an effective bench to bedside transfer in hepatology. This article is protected by copyright. All rights reserved.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_124,

title = {Mapping of the Human Placenta: Experimental Evidence of Amniotic Epithelial Cell Heterogeneity.},

author = {Centurione L and Passaretta F and Centurione MA and Munari S and Vertua E and Silini A and Liberati M and Parolini O and Pietro RD},

url = {http://journals.sagepub.com/doi/abs/10.1177/0963689717725078?url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org&rfr_dat=cr_pub%3Dpubmed&},

doi = {10.1177/0963689717725078},

year  = {2018},

date = {2018-01-31},

journal = {Cell transplantation},

volume = {27},

number = {1},

pages = {12-22},

abstract = {The human placenta is an important source of stem cells that can be easily collected without ethical concerns since it is usually discarded after childbirth. In this study, we analyzed the amniotic membrane (AM) from the human placenta with the aim of mapping different regions with respect to their morpho-functional features and regenerative potential. AMs were obtained from 24 healthy women, undergoing a caesarean section, and mapped into 4 different regions according to their position in relation to the umbilical cord: the central, intermediate, peripheral, and reflected areas. We carried out a multiparametric analysis focusing our attention on amniotic epithelial cells (AECs). Our results revealed that AECs, isolated from the different areas, are a heterogeneous cell population with different pluripotency and proliferation marker expression (octamer-binding transcription factor 4 [OCT-4], tyrosine-protein kinase KIT [c-KIT], sex determining region Y-box 2 [SOX-2], alpha-fetoprotein, cyclic AMP response element binding [CREB] protein, and phosphorylated active form of CREB [p-CREB]), proliferative ability, and osteogenic potential. Our investigation discloses interesting findings that could be useful for increasing the efficiency of AM isolation and application for therapeutic purposes.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_136,

title = {Therapeutic Targeting of mTOR in T-Cell Acute Lymphoblastic Leukemia: An Update.},

author = {Evangelisti C and Chiarini F and McCubrey JA and Martelli AM},

url = {https://www.mdpi.com/1422-0067/19/7/1878},

doi = {10.3390/ijms19071878},

year  = {2018},

date = {2018-01-26},

journal = {International journal of molecular sciences},

volume = {19},

number = {7},

pages = {pii: E1878},

abstract = {T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive blood malignancy that arises from the clonal expansion of transformed T-cell precursors. Although T-ALL prognosis has significantly improved due to the development of intensive chemotherapeutic protocols, primary drug-resistant and relapsed patients still display a dismal outcome. In addition, lifelong irreversible late effects from conventional therapy are a growing problem for leukemia survivors. Therefore, novel targeted therapies are required to improve the prognosis of high-risk patients. The mechanistic target of rapamycin (mTOR) is the kinase subunit of two structurally and functionally distinct multiprotein complexes, which are referred to as mTOR complex 1 (mTORC1) and mTORC2. These two complexes regulate a variety of physiological cellular processes including protein, lipid, and nucleotide synthesis, as well as autophagy in response to external cues. However, mTOR activity is frequently deregulated in cancer, where it plays a key oncogenetic role driving tumor cell proliferation, survival, metabolic transformation, and metastatic potential. Promising preclinical studies using mTOR inhibitors have demonstrated efficacy in many human cancer types, including T-ALL. Here, we highlight our current knowledge of mTOR signaling and inhibitors in T-ALL, with an emphasis on emerging evidence of the superior efficacy of combinations consisting of mTOR inhibitors and either traditional or targeted therapeutics.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_121,

title = {Therapeutic targeting of CK2 in acute and chronic leukemias.},

author = {Buontempo F and McCubrey JA and Orsini E and Ruzzene M and Cappellini A and Lonetti A and Evangelisti C and Chiarini F and Evangelisti C and Barata JT and Martelli AM},

url = {https://www.nature.com/articles/leu2017301},

doi = {10.1038/leu.2017.301},

year  = {2018},

date = {2018-01-11},

journal = {Leukemia},

volume = {32},

number = {1},

pages = {1-10},

abstract = {CK2 is a ubiquitously expressed, constitutively active Ser/Thr protein kinase, which is considered the most pleiotropic protein kinase in the human kinome. Such a pleiotropy explains the involvement of CK2 in many cellular events. However, its predominant roles are stimulation of cell growth and prevention of apoptosis. High levels of CK2 messenger RNA and protein are associated with CK2 pathological functions in human cancers. Over the last decade, basic and translational studies have provided evidence of CK2 as a pivotal molecule driving the growth of different blood malignancies. CK2 overexpression has been demonstrated in nearly all the types of hematological cancers, including acute and chronic leukemias, where CK2 is a key regulator of signaling networks critical for cell proliferation, survival and drug resistance. The findings that emerged from these studies suggest that CK2 could be a valuable therapeutic target in leukemias and supported the initiation of clinical trials using CK2 antagonists. In this review, we summarize the recent advances on the understanding of the signaling pathways involved in CK2 inhibition-mediated effects with a particular emphasis on the combinatorial use of CK2 inhibitors as novel therapeutic strategies for treating both acute and chronic leukemia patients.Leukemia advance online publication, 24 October 2017},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_232,

title = {MiRNA-210: A Current Overview.},

author = {Bavelloni A and Ramazzotti G and Poli A and Piazzi M and Focaccia E and Blalock WL and Faenza I},

url = {http://ar.iiarjournals.org/content/37/12/6511.long},

year  = {2017},

date = {2017-12-18},

urldate = {2017-12-18},

journal = {Anticancer Research},

volume = {37},

number = {12},

pages = {6511-6521},

abstract = {microRNAs (miRNAs) are a group of highly conserved small non-coding RNAs that were found to enhance mRNA degradation or inhibit post-transcriptional translation. Accumulating evidence indicates that miRNAs contribute to tumorigenesis and cancer metastasis. microRNA-210 has been largely studied in the past several years and has been identified as a major miRNA induced under hypoxia. A variety of miR-210 targets have been identified pointing to its role, not only in mitochondrial metabolism, but also in angiogenesis, the DNA damage response, cell proliferation, and apoptosis. Based on earlier research findings, this review aims to provide a current overview on the involvement of miRNA-210 in biological processes and diseases.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_238,

title = {Relation between circulating oxidized-LDL and metabolic syndrome in children with obesity: the role of hypertriglyceridemic waist phenotype.},

author = {Calcaterra V and De Giuseppe R and Biino G and Mantelli M and Marchini S and Bendotti G and Madè A and Avanzini MA and Montalbano C and Cossellu G and Larizza D and Cena H},

url = {https://www.degruyter.com/view/j/jpem.ahead-of-print/jpem-2017-0239/jpem-2017-0239.xml},

doi = {doi.org/10.1515/jpem-2017-0239},

year  = {2017},

date = {2017-11-27},

journal = {Journal of pediatric endocrinology and metabolism},

volume = {30},

number = {12},

pages = {1257-1263},

abstract = {BACKGROUND: The association between oxidative stress (OS) and metabolic syndrome (MetS) has been reported in adults. We analyzed the relation between circulating oxidized low-density lipoproteins (Ox-LDL) and MetS in pediatric ages in order to define whether plasma Ox-LDL levels are correlated to obesity and whether oxidative damage, using serum Ox-LDL levels as a proxy, are associated with MetS. METHODS: We enrolled 178 children (11.8±2.6 years). On the basis of a body mass index (BMI) threshold, the subjects were classified as: normal weight BMI <75th percentile; overweight BMI 75-97th percentile; obese BMI >97th percentile. Patients were classified as having MetS if they met three or more of the following criteria for age and sex: BMI >97th percentile, triglyceride levels >95th percentile, high-density lipoprotein (HDL) cholesterol level <5th percentile, systolic blood pressure (SBP) and/or diastolic blood pressure (DBP) >95th percentile and impaired glucose tolerance. RESULTS: Obese children showed increased MetS prevalence (p=0.001) and higher Ox-LDL levels compared to normal- and overweight subjects (p<0.05), with a limited relation between Ox-LDL and MetS (p=0.06). Waist-to-height ratio (W/HtR) (p=0.02), triglycerides (TG) (p=0.001) and LDL-cholesterol (p<0.001) resulted independent predictors of increased plasma Ox-LDL levels. CONCLUSIONS: Oxidative damage was correlated with a hypertriglyceridemic waist phenotype and can be a precocious marker of MetS and cardiometabolic risk in obese children.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_224,

title = {Living on the Edge: DNA Polymerase Lambda between Genome Stability and Mutagenesis.},

author = {van Loon B and Hubscher U and Maga G},

url = {http://pubs.acs.org/doi/abs/10.1021/acs.chemrestox.7b00152},

doi = {10.1021/acs.chemrestox.7b00152},

year  = {2017},

date = {2017-11-20},

journal = {Chemical research in toxicology},

volume = {30},

number = {11},

pages = {1936-1941},

abstract = {In human cells, only four DNA polymerases (pols) are necessary and sufficient for the duplication of the genetic information. However, more than a dozen DNA pols are required to maintain its integrity. Such a high degree of specialization makes DNA repair pols able to cope with specific lesions or repair pathways. On the other hand, the same DNA pols can have partially overlapping roles, which could result in possible conflicts of functions, if the DNA pols are not properly regulated. DNA pol λ is a typical example of such an enzyme. It is a multifunctional enzyme, endowed with special structural and biochemical properties, which make it capable of participating in different DNA repair pathways such as base excision repair, nonhomologous end joining, and translesion synthesis. However, when mutated or deregulated, DNA pol λ can also be a source of genetic instability. Its multiple roles in DNA damage tolerance and its ability in promoting tumor progression make it also a possible target for novel anticancer approaches.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_218,

title = {Human White Adipocytes Convert Into "Rainbow" Adipocytes In Vitro.},

author = {Maurizi G and Poloni A and Mattiucci D and Santi S and Maurizi A and Izzi V and Giuliani A and Mancini S and Zingaretti MC and Perugini J and Severi I and Falconi M and Vivarelli M and Rippo MR and Corvera S and Giordano A and Leoni P and Cinti S},

url = {http://onlinelibrary.wiley.com/doi/10.1002/jcp.25743/abstract},

doi = {10.1002/jcp.25743.},

year  = {2017},

date = {2017-10-28},

journal = {Journal of cellular physiology},

volume = {232},

number = {10},

pages = {2887-2899},

abstract = {White adipocytes are plastic cells able to reversibly transdifferentiate into brown adipocytes and into epithelial glandular cells under physiologic stimuli in vivo. These plastic properties could be used in future for regenerative medicine, but are incompletely explored in their details. Here, we focused on plastic properties of human mature adipocytes (MA) combining gene expression profile through microarray analysis with morphologic data obtained by electron and time lapse microscopy. Primary MA showed the classic morphology and gene expression profile of functional mature adipocytes. Notably, despite their committed status, MA expressed high levels of reprogramming genes. MA from ceiling cultures underwent transdifferentiation toward fibroblast-like cells with a well-differentiated morphology and maintaining stem cell gene signatures. The main morphologic aspect of the transdifferentiation process was the secretion of large lipid droplets and the development of organelles necessary for exocrine secretion further supported the liposecretion process. Of note, electron microscope findings suggesting liposecretion phenomena were found also in explants of human fat and rarely in vivo in fat biopsies from obese patients. In conclusion, both MA and post-liposecretion adipocytes show a well-differentiated phenotype with stem cell properties in line with the extraordinary plasticity of adipocytes in vivo. J. Cell. Physiol. 232: 2887-2899, 2017. 2016 Wiley Periodicals, Inc.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_207,

title = {Transcription and DNA Damage: Holding Hands or Crossing Swords? First dual AK/GSK-3beta inhibitors endowed with antioxidant properties as multifunctional, potential neuroprotective agents.},

author = {D'Alessandro G and {d'Adda di Fagagna F}},

url = {http://www.sciencedirect.com/science/article/pii/S0022283616304715?via%3Dihub},

doi = {10.1016/j.jmb.2016.11.002},

year  = {2017},

date = {2017-10-27},

journal = {Journal of Molecular Biology},

volume = {429},

number = {21},

pages = {3215-3229},

abstract = {Transcription has classically been considered a potential threat to genome integrity. Collision between transcription and DNA replication machinery, and retention of DNA:RNA hybrids, may result in genome instability. On the other hand, it has been proposed that active genes repair faster and preferentially via homologous recombination. Moreover, while canonical transcription is inhibited in the proximity of DNA double-strand breaks, a growing body of evidence supports active non-canonical transcription at DNA damage sites. Small non-coding RNAs accumulate at DNA double-strand break sites in mammals and other organisms, and are involved in DNA damage signaling and repair. Furthermore, RNA binding proteins are recruited to DNA damage sites and participate in the DNA damage response. Here, we discuss the impact of transcription on genome stability, the role of RNA binding proteins at DNA damage sites, and the function of small non-coding RNAs generated upon damage in the signaling and repair of DNA lesions.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_408,

title = {Telomerase abrogates aneuploidy-induced telomere replication stress, senescence and cell depletion.},

author = {Meena JK and Cerutti A and Beichler C and Morita Y and Bruhn C and Kumar M and Kraus JM and Speicher MR and Wang ZQ and Kestler HA and {d'Adda di Fagagna F} and Günes C and Rudolph KL},

url = {https://www.embopress.org/doi/full/10.15252/embj.201490070},

doi = {10.15252/embj.201490070},

year  = {2017},

date = {2017-10-13},

journal = {Embo Journal},

volume = {34},

number = {10},

pages = {1371-1384},

abstract = {The causal role of aneuploidy in cancer initiation remains under debate since mutations of euploidy-controlling genes reduce cell fitness but aneuploidy strongly associates with human cancers. Telomerase activation allows immortal growth by stabilizing telomere length, but its role in aneuploidy survival has not been characterized. Here, we analyze the response of primary human cells and murine hematopoietic stem cells (HSCs) to aneuploidy induction and the role of telomeres and the telomerase in this process. The study shows that aneuploidy induces replication stress at telomeres leading to telomeric DNA damage and p53 activation. This results in p53/Rb-dependent, premature senescence of human fibroblast, and in the depletion of hematopoietic cells in telomerase-deficient mice. Endogenous telomerase expression in HSCs and enforced expression of telomerase in human fibroblasts are sufficient to abrogate aneuploidy-induced replication stress at telomeres and the consequent induction of premature senescence and hematopoietic cell depletion. Together, these results identify telomerase as an aneuploidy survival factor in mammalian cells based on its capacity to alleviate telomere replication stress in response to aneuploidy induction. 2015 The Authors.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_187,

title = {Genome-wide meta-analysis associates HLA-DQA1/DRB1 and LPA and lifestyle factors with human longevity.},

author = {Joshi PK and Pirastu N and Kentistou KA and Fischer K and Hofer E and {et al} and Biino G and {et al} and Hayward C and Chasman D and Martin NG and Sattar N and Campbell H and Esko T and Kutalik Z and Wilson JF},

url = {https://www.nature.com/articles/s41467-017-00934-5},

doi = {10.1038/s41467-017-00934-5},

year  = {2017},

date = {2017-10-13},

journal = {Nature Communications},

volume = {8},

number = {1},

pages = {910},

abstract = {Genomic analysis of longevity offers the potential to illuminate the biology of human aging. Here, using genome-wide association meta-analysis of 606,059 parents' survival, we discover two regions associated with longevity (HLA-DQA1/DRB1 and LPA). We also validate previous suggestions that APOE, CHRNA3/5, CDKN2A/B, SH2B3 and FOXO3A influence longevity. Next we show that giving up smoking, educational attainment, openness to new experience and high-density lipoprotein (HDL) cholesterol levels are most positively genetically correlated with lifespan while susceptibility to coronary artery disease (CAD), cigarettes smoked per day, lung cancer, insulin resistance and body fat are most negatively correlated. We suggest that the effect of education on lifespan is principally mediated through smoking while the effect of obesity appears to act via CAD. Using instrumental variables, we suggest that an increase of one body mass index unit reduces lifespan by 7 months while 1 year of education adds 11 months to expected lifespan.Variability in human longevity is genetically influenced. Using genetic data of parental lifespan, the authors identify associations at HLA-DQA/DRB1 and LPA and find that genetic variants that increase educational attainment have a positive effect on lifespan whereas increasing BMI negatively affects lifespan.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_215,

title = {Glycogen Synthase Kinase-3beta Inhibition Links Mitochondrial Dysfunction, Extracellular Matrix Remodelling and Terminal Differentiation in Chondrocytes.},

author = {Guidotti S and Minguzzi M and Platano D and Santi S and Trisolino G and Filardo G and Mariani E and Borzì RM},

url = {www.nature.com/articles/s41598-017-12129-5},

doi = {10.1038/s41598-017-12129-5},

year  = {2017},

date = {2017-09-21},

journal = {Scientific reports},

volume = {7},

number = {1},

pages = {12059},

abstract = {Following inflammatory stimuli, GSK3 inhibition functions as a hub with pleiotropic effects leading to cartilage degradation. However, little is known about the effects triggered by its direct inhibition as well as the effects on mitochondrial pathology, that contributes to osteoarthritis pathogenesis. To this aim we assessed the molecular mechanisms triggered by GSK3β inactivating stimuli on 3-D (micromass) cultures of human articular chondrocytes. Stimuli were delivered either at micromass seeding (long term) or after maturation (short term) to explore "late" effects on terminal differentiation or "early" mitochondrial effects, respectively. GSK3β inhibition significantly enhanced mitochondrial oxidative stress and damage and endochondral ossification based on increased nuclear translocation of Runx-2 and β-catenin, calcium deposition, cell death and enhanced remodelling of the extracellular matrix as demonstrated by the increased collagenolytic activity of supernatants, despite unmodified (MMP-1) or even reduced (MMP-13) collagenase gene/protein expression. Molecular dissection of the underlying mechanisms showed that GSK3β inhibition achieved with pharmacological/silencing strategies impacted on the control of collagenolytic activity, via both decreased inhibition (reduced TIMP-3) and increased activation (increased MMP-10 and MMP-14). To conclude, the inhibition of GSK3β enhances terminal differentiation via concerted effects on ECM and therefore its activity represents a tool to keep articular cartilage homeostasis.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_189,

title = {Phosphorylation regulates human pol-eta stability and damage bypass throughout the cell cycle.},

author = {Bertoletti F and Cea V and Liang CC and Lanati T and Maffia A and Avarello MDM and Cipolla L and Lehmann AR and Cohn MA and Sabbioneda S},

url = {https://academic.oup.com/nar/article/45/16/9441/4002723},

doi = {10.1093/nar/gkx619},

year  = {2017},

date = {2017-09-19},

journal = {Nucleic Acids Research},

volume = {45},

number = {16},

pages = {9441-9454},

abstract = {DNA translesion synthesis (TLS) is a crucial damage tolerance pathway that oversees the completion of DNA replication in the presence of DNA damage. TLS polymerases are capable of bypassing a distorted template but they are generally considered inaccurate and they need to be tightly regulated. We have previously shown that pol-eta is phosphorylated on Serine 601 after DNA damage and we have demonstrated that this modification is important for efficient damage bypass. Here we report that pol-eta is also phosphorylated by CDK2, in the absence of damage, in a cell cycle-dependent manner and we identify serine 687 as an important residue targeted by the kinase. We discover that phosphorylation on serine 687 regulates the stability of the polymerase during the cell cycle, allowing it to accumulate in late S and G2 when productive TLS is critical for cell survival. Furthermore, we show that alongside the phosphorylation of S601, the phosphorylation of S687 and S510, S512 and/or S514 are important for damage bypass and cell survival after UV irradiation. Taken together our results provide new insights into how cells can, at different times, modulate DNA TLS for improved cell survival.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_194,

title = {Recent Advancements in DNA Damage-Transcription Crosstalk and High-Resolution Mapping of DNA Breaks.},

author = {Vitelli V and Galbiati A and Iannelli F and Pessina F and Sharma S and {d'Adda di Fagagna F}},

url = {http://www.annualreviews.org/doi/full/10.1146/annurev-genom-091416-035314?url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org&rfr_dat=cr_pub%3Dpubmed&},

doi = {10.1146/annurev-genom-091416-035314},

year  = {2017},

date = {2017-08-31},

journal = {Annual review of genomics and human genetics},

volume = {18},

pages = {87-113},

abstract = {"Until recently, DNA damage arising from physiological DNA metabolism was considered a detrimental by-product for cells. However, an increasing amount of evidence has shown that DNA damage could have a positive role in transcription activation. In particular, DNA damage has been detected in transcriptional elements following different stimuli. These physiological DNA breaks are thought to be instrumental for the correct expression of genomic loci through different mechanisms. In this regard, although a plethora of methods are available to precisely map transcribed regions and transcription start sites, commonly used techniques for mapping DNA breaks lack sufficient resolution and sensitivity to draw a robust correlation between DNA damage generation and transcription. Recently, however, several methods have been developed to map DNA damage at single-nucleotide resolution, thus providing a new set of tools to correlate DNA damage and transcription. Here, we review how DNA damage can positively regulate transcription initiation, the current techniques for mapping DNA breaks at high resolution, and how these techniques can benefit future studies of DNA damage and transcription.

"},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_200,

title = {Genome-wide DNA methylation analysis in blood cells from patients with Werner syndrome.},

author = {Guastafierro T and Bacalini MG and Marcoccia A and Gentilini D and Pisoni S and Di Blasio AM and Corsi A and Franceschi C and Raimondo D and Spanò A and Garagnani P and Bondanini F},

url = {https://clinicalepigeneticsjournal.biomedcentral.com/articles/10.1186/s13148-017-0389-4},

doi = {10.1186/s13148-017-0389-4},

year  = {2017},

date = {2017-08-30},

journal = {Clinical epigenetics},

volume = {9},

pages = {92},

abstract = {BACKGROUND: Werner syndrome is a progeroid disorder characterized by premature age-related phenotypes. Although it is well established that autosomal recessive mutations in the WRN gene is responsible for Werner syndrome, the molecular alterations that lead to disease phenotype remain still unidentified. RESULTS: To address whether epigenetic changes can be associated with Werner syndrome phenotype, we analysed genome-wide DNA methylation profile using the Infinium MethylationEPIC BeadChip in the whole blood from three patients affected by Werner syndrome compared with three age- and sex-matched healthy controls. Hypermethylated probes were enriched in glycosphingolipid biosynthesis, FoxO signalling and insulin signalling pathways, while hypomethylated probes were enriched in PI3K-Akt signalling and focal adhesion pathways. Twenty-two out of 47 of the differentially methylated genes belonging to the enriched pathways resulted differentially expressed in a publicly available dataset on Werner syndrome fibroblasts. Interestingly, differentially methylated regions identified CERS1 and CERS3, two members of the ceramide synthase family. Moreover, we found differentially methylated probes within ITGA9 and ADAM12 genes, whose methylation is altered in systemic sclerosis, and within the PRDM8 gene, whose methylation is affected in dyskeratosis congenita and Down syndrome. CONCLUSIONS: DNA methylation changes in the peripheral blood from Werner syndrome patients provide new insight in the pathogenesis of the disease, highlighting in some cases a functional correlation of gene expression and methylation status.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}