@article{%a1:%Y_360,

title = {Epicardial fat thickness: threshold values and lifestyle association in male adolescents.},

author = {Cena H and Fonte ML and Casali PM and Maffoni S and Roggi C and Biino G},

url = {https://onlinelibrary.wiley.com/doi/full/10.1111/ijpo.227},

doi = {10.1111/ijpo.227},

year  = {2015},

date = {2015-04-10},

journal = {Pediatric Obesity},

volume = {10},

number = {2},

pages = {105-111},

abstract = {BACKGROUND: Obese adolescents with high proportion of visceral fat are at higher risk of developing the metabolic syndrome. OBJECTIVES: The study aims to investigate if echocardiographic epicardial fat thickness (EF) could be predictive of visceral obesity (VO) early in life and to provide EF threshold values specific for male adolescents. Further aim was to investigate the association between EF, lifestyle and metabolic disease familiarity. METHODS: Anthropometric data were collected from 102 normal weight and overweight, healthy male adolescents (mean age: 14.91 +/-  1.98 years); bioelectrical impedance analysis and transthoracic echocardiogram were performed in the same sample. Each participant fulfilled a validated self-administered lifestyle questionnaire. RESULTS: We found higher EF values in sedentary adolescents (P < 0.05), in those who never eat fruit and vegetables (P < 0.05), and in those with overweight mothers (P < 0.05). The strongest independent predictor of EF was waist circumference (P < 0.0001). Using the waist to height ratio as a marker of VO, logistic regression analysis revealed that 1 mm EF gain is responsible for seven times higher VO risk (P < 0.0001). Receiver Operating Characteristic (ROC) analysis showed that the optimal cut-off for EF thickness associated to youth VO is 3.2 mm.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_381,

title = {Modulation of TGFbeta 2 levels by lamin A in U2-OS osteoblast-like cells: understanding the osteolytic process triggered by altered lamins.},

author = {Evangelisti C and Bernasconi P and Cavalcante P and Cappelletti C and D'Apice MR and Sbraccia P and Novelli G and Prencipe S and Lemma S and Baldini N and Avnet S and Squarzoni S and Martelli AM and Lattanzi G},

url = {http://www.oncotarget.com/index.php?journal=oncotarget&page=article&op=view&path[]=3232&pubmed-linkout=1},

year  = {2015},

date = {2015-04-10},

journal = {Oncotarget},

volume = {6},

number = {10},

pages = {7424-7437},

abstract = {Transforming growth factor beta (TGFbeta) plays an essential role in bone homeostasis and deregulation of TGFbeta occurs in bone pathologies. Patients affected by Mandibuloacral Dysplasia (MADA), a progeroid disease linked to LMNA mutations, suffer from an osteolytic process. Our previous work showed that MADA osteoblasts secrete excess amount of TGFbeta 2, which in turn elicits differentiation of human blood precursors into osteoclasts. Here, we sought to determine how altered lamin A affects TGFbeta signaling. Our results show that wild-type lamin A negatively modulates TGFbeta 2 levels in osteoblast-like U2-OS cells, while the R527H mutated prelamin A as well as farnesylated prelamin A do not, ultimately leading to increased secretion of TGFbeta 2. TGFbeta 2 in turn, triggers the Akt/mTOR pathway and upregulates osteoprotegerin and cathepsin K. TGFbeta 2 neutralization rescues Akt/mTOR activation and the downstream transcriptional effects, an effect also obtained by statins or RAD001 treatment. Our results unravel an unexpected role of lamin A in TGFbeta 2 regulation and indicate rapamycin analogs and neutralizing antibodies to TGFbeta 2 as new potential therapeutic tools for MADA.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_400,

title = {Reference genes for gene expression analysis in proliferating and differentiating human keratinocytes.},

author = {Lanzafame M and Botta E and Teson M and Fortugno P and Zambruno G and Stefanini M and Orioli D},

url = {https://iubmb.onlinelibrary.wiley.com/doi/full/10.1002/iub.1366},

doi = {10.1002/iub.1366},

year  = {2015},

date = {2015-04-07},

journal = {Experimental Dermatology},

volume = {24},

number = {4},

abstract = {Abnormalities in keratinocyte growth and differentiation have a pathogenic significance in many skin disorders and result in gene expression alterations detectable by quantitative real-time RT-PCR (qRT-PCR). Relative quantification based on endogenous control (EC) genes is the commonly adopted approach, and the use of multiple reference genes from independent pathways is considered a best practice guideline, unless fully validated EC genes are available. The literature on optimal reference genes during in vitro calcium-induced differentiation of normal human epidermal keratinocytes (NHEK) is inconsistent. In many studies, the expression of target genes is compared to that of housekeeping genes whose expression, however, significantly varies during keratinocyte differentiation. Here, we report the results of our investigations on the expression stability of 15 candidate EC genes, including those commonly used as reference in expression analysis by qRT-PCR, during NHEK calcium-induced differentiation. We demonstrate that YWHAZ and UBC are extremely stable genes, and therefore, they represent optimal EC genes for expression studies in proliferating and calcium-induced differentiating NHEK. Furthermore, we demonstrate that YWHAZ/14-3-3-zeta is a suitable reference for quantitative comparison of both transcript and protein levels. 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_386,

title = {NF-kB mediated down-regulation of collagen synthesis upon HEMA (2-hydroxyethyl methacrylate) treatment of primary human gingival fibroblast/Streptococcus mutans co-cultured cells.},

author = {Grande R and Pacella S and Di Giulio M and Rapino M and Di Valerio V and Cellini L and Cataldi A},

url = {https://link.springer.com/article/10.1007%2Fs00784-014-1304-4},

doi = {10.1007/s00784-014-1304-4},

year  = {2015},

date = {2015-03-25},

journal = {Clinical Oral Investigations},

volume = {19},

number = {4},

abstract = {PURPOSE: In vitro studies have evidenced the cytotoxic effect of HEMA (2-hydroxyethyl methacrylate), the most common component of dental resin-based restorative material, which is released within the oral cavity, on eukaryotic cells such as gingival fibroblast and epithelial cells. However, since the presence of microorganisms within the oral cavity cannot be excluded and little is known about the interactions occurring between eukaryotic cells and the human oral microbiota, our attention has been addressed to investigate the effect of 3 mM HEMA on the molecular mechanisms driving the response of human gingival fibroblasts (HGFs) co-cultured with Streptococcus mutans. METHODOLOGY:HGF/S. mutans co-culture has been set up in our lab, and upon HEMA treatment, S.mutans and HGF cells' viability and adhesion along with type I collagen gene and pro-collagen I, Bax, Bcl2, nuclear factor kB (NF-kB), IkBα, pIkBα protein expression by PCR, Western blotting and ELISA assays have been investigated. RESULTS:HEMA treatment determines a significant decrease of type I collagen protein production, even in the presence of S. mutans, in parallel to a decrease of cell viability and adhesion, which seem to be regulated by NF-kB activation. In fact, when SN50, NF-kB-specific pharmacological inhibitor, is added to the culture, cell proliferation along with collagen synthesis is restored. CONCLUSION: The modulation exerted by S. mutans on the cytotoxic effect of HEMA suggests that within the oral cavity, the eukaryotic/prokaryotic cell interactions, maintaining the balance of the environment, allow HEMA to perform its adhesive and bonding function and that the use of a co-culture system, which simulates the oral cavity organization, improves the knowledge concerning the biocompatibility of this dental material.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_362,

title = {FSH and LH receptors are differentially expressed in cumulus cells surrounding developmentally competent and incompetent mouse fully grown antral oocytes.},

author = {Vigone G and Merico V and Redi CA and Mazzini G and Garagna S and Zuccotti M},

doi = {10.1071/RD13251},

year  = {2015},

date = {2015-03-19},

journal = {Reproduction, fertility and development},

volume = {27},

number = {3},

pages = {497-503},

abstract = {Cumulus cells (CCs) maintain strict functional relationships with the enclosed antral oocyte and are thought to reflect its developmental competence. Several studies have described a correlation between CC gene expression and oocyte quality. Herein, we tested whether CC-specific FSH and LH receptors (FSHR and LHR, respectively) are differentially expressed in CCs enclosing developmentally competent or incompetent oocytes. To this end, mouse fully grown cumulus-oocyte complexes were isolated and their CCs and oocytes analysed separately. Based on their chromatin organisation, oocytes were classified as those with a surrounded nucleolus (SN) or a non-surrounded nucleolus (NSN), the former being developmentally competent, whereas the latter arrest at the 2-cell stage. The CCs were then analysed to compare the pattern of expression of the Fshr and Lhr genes and their proteins. Quantitative reverse transcription-polymerase chain reaction analysis revealed that only Lhr is significantly differentially expressed. Immunofluorescence analysis revealed that both FSHR and LHR proteins are significantly upregulated in CCs surrounding oocytes arrested at the 2-cell stage, reflecting their developmental incompetence.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_387,

title = {Notch is a direct negative regulator of the DNA-damage response.},

author = {Vermezovic J and Adamowicz M and Santarpia L and Rustighi A and Forcato M and Lucano C and Massimiliano L and Costanzo V and Bicciato S and Del Sal G and {d'Adda di Fagagna F}},

url = {https://www.nature.com/articles/nsmb.3013},

doi = {10.1038/nsmb.3013},

year  = {2015},

date = {2015-03-14},

journal = {Nature Structural & Molecular Biology},

volume = {22},

number = {5},

pages = {417-424},

abstract = {The DNA-damage response (DDR) ensures genome stability and proper inheritance of genetic information, both of which are essential to survival. It is presently unclear to what extent other signaling pathways modulate DDR function. Here we show that Notch receptor binds and inactivates ATM kinase and that this mechanism is evolutionarily conserved in Caenorhabditis elegans, Xenopus laevis and humans. In C. elegans, the Notch pathway impairs DDR signaling in gonad germ cells. In mammalian cells, activation of human Notch1 leads to reduced ATM signaling in a manner independent of Notch1 transcriptional activity. Notch1 binds directly to the regulatory FATC domain of ATM and inhibits ATM kinase activity. Notch1 and ATM activation are inversely correlated in human breast cancers, and inactivation of ATM by Notch1 contributes to the survival of Notch1-driven leukemia cells upon DNA damage.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_379,

title = {Metabolic reprogramming and dysregulated metabolism: cause, consequence and/or enabler of environmental carcinogenesis?},

author = {Robey RB and Weisz J and Kuemmerle NB and Salzberg AC and Berg A and Brown DG and Kubik L and Palorini R and Al-Mulla F and Al-Temaimi R and Colacci A and Mondello C and Raju J and Woodrick J and Scovassi AI and Singh N and Vaccari M and Roy R and Forte S and Memeo L and Salem HK and Amedei A and Hamid RA and Williams GP and Lowe L and Meyer J and Martin FL and Bisson WH and Chiaradonna F and Ryan EP},

url = {https://academic.oup.com/carcin/article/36/Suppl_1/S203/316346},

doi = {10.1093/carcin/bgv037},

year  = {2015},

date = {2015-03-13},

journal = {Carcinogenesis},

volume = {36},

number = {Suppl. 1},

pages = {S203-231},

abstract = {Environmental contributions to cancer development are widely accepted, but only a fraction of all pertinent exposures have probably been identified. Traditional toxicological approaches to the problem have largely focused on the effects of individual agents at singular endpoints. As such, they have incompletely addressed both the pro-carcinogenic contributions of environmentally relevant low-dose chemical mixtures and the fact that exposures can influence multiple cancer-associated endpoints over varying timescales. Of these endpoints, dysregulated metabolism is one of the most common and recognizable features of cancer, but its specific roles in exposure-associated cancer development remain poorly understood. Most studies have focused on discrete aspects of cancer metabolism and have incompletely considered both its dynamic integrated nature and the complex controlling influences of substrate availability, external trophic signals and environmental conditions. Emerging high throughput approaches to environmental risk assessment also do not directly address the metabolic causes or consequences of changes in gene expression. As such, there is a compelling need to establish common or complementary frameworks for further exploration that experimentally and conceptually consider the gestalt of cancer metabolism and its causal relationships to both carcinogenesis and the development of other cancer hallmarks. A literature review to identify environmentally relevant exposures unambiguously linked to both cancer development and dysregulated metabolism suggests major gaps in our understanding of exposure-associated carcinogenesis and metabolic reprogramming. Although limited evidence exists to support primary causal roles for metabolism in carcinogenesis, the universality of altered cancer metabolism underscores its fundamental biological importance, and multiple pleiomorphic, even dichotomous, roles for metabolism in promoting, antagonizing or otherwise enabling the development and selection of cancer are suggested. Published by Oxford University Press 2015.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_418,

title = {Unconventional Knoevenagel-type indoles: Synthesis and cell-based studies for the identification of pro-apoptotic agents.},

author = {Spallarossa A and Caneva C and Caviglia M and Alfei S and Butini S and Campiani G and Gemma S and Brindisi M and Zisterer DM and Bright SA and Williams CD and Crespan E and Maga G and Sanna G and Delogu I and Collu G and Loddo R},

url = {https://www.sciencedirect.com/science/article/pii/S0223523415301938?via%3Dihub},

doi = {10.1016/j.ejmech.2015.08.009},

year  = {2015},

date = {2015-03-12},

urldate = {2017-03-03},

journal = {European Journal of Medicinal Chemistry},

volume = {102},

pages = {648-660},

abstract = {A new series of indole-based analogues were recently identified as potential anticancer agents. The Knoevenagel-type indoles herein presented were prepared via a one-pot condensation of iminium salts with active methylene reagents and were isolated as single geometric isomers. Biological evaluation in different cell-based assays revealed an antiproliferative activity for some analogues already in the nanomolar range against leukaemia, breast and renal cancer cell lines. To explain these effects, the most promising analogues of the series were engaged in further cell-based studies. Compounds 5e, l, p and 6a, b highlighted a pro-apoptotic potential being able to induce apoptosis in HL60, K562 and MCF-7 cell lines in a dose and time-dependent manner. The ability of these compounds to arrest cell cycle at the G2/M phase inspired the immunofluorescence studies which allowed us to identify tubulin as a potential target for compounds 5l and 6b. Copyright 2015 Elsevier Masson SAS. All rights reserved.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_407,

title = {Sound representation in higher language areas during language generation.},

author = {Magrassi L and Aromataris G and Cabrini A and Annovazzi-Lodi V and Moro A},

url = {https://www.pnas.org/content/112/6/1868.long},

doi = {10.1073/pnas.1418162112},

year  = {2015},

date = {2015-03-11},

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

volume = {112},

number = {6},

pages = {1868-1873},

abstract = {How language is encoded by neural activity in the higher-level language areas of humans is still largely unknown. We investigated whether the electrophysiological activity of Broca’s area correlates with the sound of the utterances produced. During speech perception, the electric cortical activity of the auditory areas correlates with the sound envelope of the utterances. In our experiment, we compared the electrocorticogram recorded during awake neurosurgical operations in Broca’s area and in the dominant temporal lobe with the sound envelope of single words versus sentences read aloud or mentally by the patients. Our results indicate that the electrocorticogram correlates with the sound envelope of the utterances, starting before any sound is produced and even in the absence of speech, when the patient is reading mentally. No correlations were found when the electrocorticogram was recorded in the superior parietal gyrus, an area not directly involved in language generation, or in Broca’s area when the participants were executing a repetitive motor task, which did not include any linguistic content, with their dominant hand. The distribution of suprathreshold correlations across frequencies of cortical activities varied whether the sound envelope derived from words or sentences. Our results suggest the activity of language areas is organized by sound when language is generated before any utterance is produced or heard.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_395,

title = {Poly(ADP-ribosylation) and neurodegenerative disorders.},

author = {Basello DA and Scovassi AI},

url = {https://www.sciencedirect.com/science/article/pii/S156772491530012X?via%3Dihub},

doi = {10.1016/j.mito.2015.07.005},

year  = {2015},

date = {2015-03-06},

journal = {Mitochondrion},

volume = {24},

pages = {56-63},

abstract = {Impaired mitochondrial structure and function are common features of neurodegenerative disorders, ultimately characterized by the death of neural cells promoted by still unknown signals. Among the possible modulators of neurodegeneration, the activation of poly(ADP-ribosylation), a post-translational modification of proteins, has been considered, being the product of the reaction, poly(ADP-ribose), a signaling molecule for different cell death paradigms. The basic properties of poly(ADP-ribosylation) are here described, focusing on the mitochondrial events; cell death paradigms such as apoptosis, parthanatos, necroptosis and mitophagy are illustrated. Finally, the promising use of poly(ADP-ribosylation) inhibitors to rescue neurodegeneration is addressed. Copyright  2015 Elsevier B.V. and Mitochondria Research Society. Published by Elsevier B.V. All rights reserved.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_412,

title = {The effect of environmental chemicals on the tumor microenvironment.},

author = {Casey SC and Vaccari M and Al-Mulla F and Al-Temaimi R and Amedei A and Barcellos-Hoff MH and Brown DG and Chapellier M and Christopher J and Curran C and Forte S and Hamid RA and Heneberg P and Koch DC and Krishnakumar PK and Laconi E and Maguer-Satta V and Marongiu F and Memeo L and Mondello C and Raju J and Roman J and Roy R and Ryan EP and Ryeom S and Salem HK and Scovassi AI and Singh N and Soucek L and Vermeulen L and Whitfield JR and Woodrick J and Colacci A and Bisson WH and Felsher DW},

url = {https://academic.oup.com/carcin/article/36/Suppl_1/S160/315417},

doi = {10.1093/carcin/bgv035},

year  = {2015},

date = {2015-03-06},

journal = {Carcinogenesis},

volume = {36},

number = {Suppl. 1},

pages = {S160-183},

abstract = {Potentially carcinogenic compounds may cause cancer through direct DNA damage or through indirect cellular or physiological effects. To study possible carcinogens, the fields of endocrinology, genetics, epigenetics, medicine, environmental health, toxicology, pharmacology and oncology must be considered. Disruptive chemicals may also contribute to multiple stages of tumor development through effects on the tumor microenvironment. In turn, the tumor microenvironment consists of a complex interaction among blood vessels that feed the tumor, the extracellular matrix that provides structural and biochemical support, signaling molecules that send messages and soluble factors such as cytokines. The tumor microenvironment also consists of many host cellular effectors including multipotent stromal cells/mesenchymal stem cells, fibroblasts, endothelial cell precursors, antigen-presenting cells, lymphocytes and innate immune cells. Carcinogens can influence the tumor microenvironment through effects on epithelial cells, the most common origin of cancer, as well as on stromal cells, extracellular matrix components and immune cells. Here, we review how environmental exposures can perturb the tumor microenvironment. We suggest a role for disrupting chemicals such as nickel chloride, Bisphenol A, butyltins, methylmercury and paraquat as well as more traditional carcinogens, such as radiation, and pharmaceuticals, such as diabetes medications, in the disruption of the tumor microenvironment. Further studies interrogating the role of chemicals and their mixtures in dose-dependent effects on the tumor microenvironment could have important general mechanistic implications for the etiology and prevention of tumorigenesis. The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_396,

title = {Posttranscriptional Regulation and RNA Binding Proteins in Cancer Biology.},

author = {Ghigna C and Cartegni L and Jordan P and Paronetto MP},

url = {https://www.hindawi.com/journals/bmri/2015/897821/},

doi = {10.1155/2015/897821},

year  = {2015},

date = {2015-03-05},

journal = {Biomed Research International},

volume = {2015},

pages = {897821},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_402,

title = {Replication of Structured DNA and its implication in epigenetic stability.},

author = {Cea V and Cipolla L and Sabbioneda S},

url = {https://www.frontiersin.org/articles/10.3389/fgene.2015.00209/full},

doi = {10.3389/fgene.2015.00209},

year  = {2015},

date = {2015-03-05},

journal = {Frontiers in Genetics},

volume = {6},

pages = {209},

abstract = {DNA replication is an extremely risky process that cells have to endure in order to correctly duplicate and segregate their genome. This task is particularly sensitive to DNA damage and multiple mechanisms have evolved to protect DNA replication as a block to the replication fork could lead to genomic instability and possibly cell death. The DNA in the genome folds, for the most part, into the canonical B-form but in some instances can form complex secondary structures such as G-quadruplexes (G4). These G rich regions are thermodynamically stable and can constitute an obstacle to DNA and RNA metabolism. The human genome contains more than 350,000 sequences potentially capable to form G-quadruplexes and these structures are involved in a variety of cellular processes such as initiation of DNA replication, telomere maintenance and control of gene expression. Only recently, we started to understand how G4 DNA poses a problem to DNA replication and how its successful bypass requires the coordinated activity of ssDNA binding proteins, helicases and specialized DNA polymerases. Their role in the resolution and replication of structured DNA crucially prevents both genetic and epigenetic instability across the genome.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_405,

title = {SAM68: Signal Transduction and RNA Metabolism in Human Cancer.},

author = {Frisone P and Pradella D and {Di Matteo A} and Belloni E and Ghigna C and Paronetto MP},

url = {https://www.hindawi.com/journals/bmri/2015/528954/},

doi = {10.1155/2015/528954},

year  = {2015},

date = {2015-03-05},

urldate = {2015-03-05},

journal = {Biomed Research International},

volume = {2015},

pages = {528954},

abstract = {Alterations in expression and/or activity of splicing factors as well as mutations in cis-acting splicing regulatory sequences contribute to cancer phenotypes. Genome-wide studies have revealed more than 15,000 tumor-associated splice variants derived from genes involved in almost every aspect of cancer cell biology, including proliferation, differentiation, cell cycle control, metabolism, apoptosis, motility, invasion, and angiogenesis. In the past decades, several RNA binding proteins (RBPs) have been implicated in tumorigenesis. SAM68 (SRC associated in mitosis of 68 kDa) belongs to the STAR (signal transduction and activation of RNA metabolism) family of RBPs. SAM68 is involved in several steps of mRNA metabolism, from transcription to alternative splicing and then to nuclear export. Moreover, SAM68 participates in signaling pathways associated with cell response to stimuli, cell cycle transitions, and viral infections. Recent evidence has linked this RBP to the onset and progression of different tumors, highlighting misregulation of SAM68-regulated splicing events as a key step in neoplastic transformation and tumor progression. Here we review recent studies on the role of SAM68 in splicing regulation and we discuss its contribution to aberrant pre-mRNA processing in cancer.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_398,

title = {Prodrugs of herpes simplex thymidine kinase inhibitors.},

author = {Yanachkova M and Xu W-C and Dvoskin S and Dix E and Yanachkov I and Savi L and Focher F and Sanchez M and Foster T and Wright G},

url = {https://journals.sagepub.com/doi/full/10.1177/2040206615608722?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%3dpubmed},

doi = {10.1177/2040206615608722},

year  = {2015},

date = {2015-03-04},

journal = {Antiviral Chemistry & Chemotherapy},

volume = {24},

number = {2},

pages = {47-55},

abstract = {Background: Because guanine-based HSV thymidine kinase inhibitors are not orally available, we synthesized various 6-deoxy prodrugs of these compounds and evaluated them with regard to solubility in water, oral bioavailability, and efficacy to prevent HSV-1 reactivation from latency in a mouse model. Methods: Organic synthesis was used to prepare compounds, HPLC to analyze hydrolytic conversion, MS to measure oral bioavailability, and mouse latent infection and induced reactivation to evaluate the efficacy of a specific prodrug.

Results: Aqueous solubilities of prodrugs were improved, oxidation of prodrugs by animal cytosols occurred in vitro, and oral absorption of the optimal prodrug sacrovirTM (6-deoxy- mCF3PG) in the presence of the aqueous adjuvant Soluplus® and conversion to active compound N2-[3-(trifluoromethyl)pheny])guanine (mCF3PG) were accomplished in mice. Treatment of HSV-1 latent mice with sacrovirTM in 1 % Soluplus in drinking water significantly suppressed HSV-1 reactivation and viral genomic replication.Conclusions: Ad libitum oral delivery of sacrovirTM was effective in suppressing HSV-1 reactivation in ocularly-infected latent mice as measured by the numbers of mice shedding infectious virus at the ocular surface, numbers of trigeminal ganglia (TG) positive for infectious virus, number of corneas that had detectable infectious virus, and HSV-1 genome copy numbers in TG following reactivation. These results demonstrate the statistically significant effect of the prodrug on suppressing HSV-1 reactivation in vivo.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_374,

title = {Inhibition of metalloproteinase activity in FANCA is linked to altered oxygen metabolism.},

author = {Ravera S and Capanni C and Tognotti D and Bottega R and Columbaro M and Dufour C and Cappelli E and Degan P},

url = {https://onlinelibrary.wiley.com/doi/full/10.1002/jcp.24778},

doi = {10.1002/jcp.24778},

year  = {2015},

date = {2015-03-03},

urldate = {2015-03-03},

journal = {Journal of Cellular Physiology},

volume = {230},

number = {3},

abstract = {Bone marrow (BM) failure, increased risk of myelodysplastic syndrome, acute leukaemia and solid tumors, endocrinopathies and congenital abnormalities are the major clinical problems in Fanconi anemia patients (FA). Chromosome instability and DNA repair defects are the cellular characteristics used for the clinical diagnosis. However, these biological defects are not sufficient to explain all the clinical phenotype of FA patients. The known defects are structural alteration in cell cytoskeleton, altered structural organization for intermediate filaments, nuclear lamina, and mitochondria. These are associated with different expression and/or maturation of the structural proteins vimentin, mitofilin, and lamin A/C suggesting the involvement of metalloproteinases (MPs). Matrix metalloproteinases (MMP) are involved in normal physiological processes such as human skeletal tissue development, maturation, and hematopoietic reconstitution after bone marrow suppression. Current observations upon the eventual role of MPs in FA cells are largely inconclusive. We evaluated the overall MPs activity in FA complementation group A (FANCA) cells by exposing them to the antioxidants N-acetyl cysteine (NAC) and resveratrol (RV). This work supports the hypothesis that treatment of Fanconi patients with antioxidants may be important in FA therapy. J. Cell. Physiol. 230: 603–609, 2015. 2014 Wiley Periodicals, Inc., A Wiley Company},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_394,

title = {PLCβ1a and PLCβ1b selective regulation and cyclin D3 modulation reduced by kinamycin F during k562 cell differentiation.},

author = {Bavelloni A and Dmitrienko GI and Goodfellow VJ and Ghavami A and Piazzi M and Blalock WL and Chiarini F and Cocco L and Faenza I},

url = {https://onlinelibrary.wiley.com/doi/full/10.1002/jcp.24776},

doi = {10.1002/jcp.24776},

year  = {2015},

date = {2015-03-03},

journal = {Journal of Cellular Physiology},

volume = {230},

number = {3},

abstract = {Here we report that both PLCβ1a and PLCβ1b are relevant regulators of erythropoiesis in that kinamycin F, a potent inducer of γ-globin production in K562 cells, caused a selectively reduction of both PLCβ1 isozymes even though the results point out that the effect of the drug is mainly directed toward the expression of the PLCβ1a isoform. We have identified a different role for the two isozymes as regulators of K562 differentiation process induced by kinamycin F. The overexpression of PLCβ1b induced an increase in γ-globin expression even in the absence of kinamycin F. Moreover during K562 differentiation, cyclin D3 level is regulated by PLCβ1 signaling pathway. Namely the amplification of the expression of the PLCβ1a, but not of PLCβ1b, is able to maintain high levels of expression of cyclin D3 even after treatment with kinamycin F. This could be due to their different distribution in the cell compartments since the amount of PLCβ1b is mainly present in the nucleus in respect to PLCβ1a. Our data indicate that the amplification of PLCβ1a expression, following treatment with kinamycin F, confers a real advantage to K562 cells viability and protects cells themselves from apoptosis.2014 Wiley Periodicals, Inc., A Wiley Company.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_330,

title = {All-trans retinoic acid and rapamycin normalize Hutchinson Gilford progeria fibroblast phenotype.},

author = {Pellegrini C and Columbaro M and Capanni C and {D'Apice MR} and Cavallo C and Murdocca M and Lattanzi G and Squarzoni S},

url = {http://www.oncotarget.com/index.php?journal=oncotarget&page=article&op=view&path[]=4939&pubmed-linkout=1},

doi = {10.18632/oncotarget.4939},

year  = {2015},

date = {2015-03-02},

urldate = {2015-03-02},

journal = {Oncotarget},

volume = {6},

number = {30},

pages = {29914-29928},

abstract = {Hutchinson Gilford progeria syndrome is a fatal disorder characterized by accelerated aging, bone resorption and atherosclerosis, caused by a LMNA mutation which produces progerin, a mutant lamin A precursor. Progeria cells display progerin and prelamin A nuclear accumulation, altered histone methylation pattern, heterochromatin loss, increased DNA damage and cell cycle alterations. Since the LMNA promoter contains a retinoic acid responsive element, we investigated if all-trans retinoic acid administration could lower progerin levels in cultured fibroblasts. We also evaluated the effect of associating rapamycin, which induces autophagic degradation of progerin and prelamin A. We demonstrate that all-trans retinoic acid acts synergistically with low-dosage rapamycin reducing progerin and prelamin A, via transcriptional downregulation associated with protein degradation, and increasing the lamin A to progerin ratio. These effects rescue cell dynamics and cellular proliferation through recovery of DNA damage response factor PARP1 and chromatin-associated nuclear envelope proteins LAP2α and BAF. The combined all-trans retinoic acid-rapamycin treatment is dramatically efficient, highly reproducible, represents a promising new approach in Hutchinson-Gilford Progeria therapy and deserves investigation in ageing-associated disorders.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_365,

title = {Genome-wide association study for refractive astigmatism reveals genetic co-determination with spherical equivalent refractive error: the CREAM consortium.},

author = {Li Q and Wojciechowski R and Simpson CL and Hysi PG and Verhoeven VJ and Ikram MK and Hohn R and Vitart V and Hewitt AW and Oexle K and Mkela KM and MacGregor S and Pirastu M and Fan Q and Cheng CY and St Pourcain B and McMahon G and Kemp JP and Northstone K and Rahi JS and Cumberland PM and Martin NG and Sanfilippo PG and Lu Y and Wang YX and Hayward C and Polasek O and Campbell H and Bencic G and Wright AF and Wedenoja J and Zeller T and Schillert A and Mirshahi A and Lackner K and Yip SP and Yap MK and Ried JS and Gieger C and Murgia F and Wilson JF and Fleck B and Yazar S and Vingerling JR and Hofman A and Uitterlinden A and Rivadeneira F and Amin N and Karssen L and Oostra BA and Zhou X and Teo YY and Tai ES and Vithana E and Barathi V and Zheng Y and Siantar RG and Neelam K and Shin Y and Lam J and Yonova-Doing E and Venturini C and Hosseini SM and Wong HS and Lehtimaki T and Kahonen M and Raitakari O and Timpson NJ and Evans DM and Khor CC and Aung T and Young TL and Mitchell P and Klein B and van Duijn CM and Meitinger T and Jonas JB and Baird PN and Mackey DA and Wong TY and Saw SM and Parssinen O and Stambolian D and Hammond CJ and Klaver CC and Williams C and Paterson AD and Bailey-Wilson JE and Guggenheim JA and CREAM Consortium},

url = {https://link.springer.com/article/10.1007%2Fs00439-014-1500-y},

doi = {10.1007/s00439-014-1500-y},

year  = {2015},

date = {2015-02-25},

journal = {Human Genetics},

volume = {134},

number = {2},

pages = {131-146},

abstract = {To identify genetic variants associated with refractive astigmatism in the general population, meta-analyses of genome-wide association studies were performed for: White Europeans aged at least 25 years (20 cohorts, N = 31,968); Asian subjects aged at least 25 years (7 cohorts, N = 9,295); White Europeans aged <25 years (4 cohorts, N = 5,640); and all independent individuals from the above three samples combined with a sample of Chinese subjects aged <25 years (N = 45,931). Participants were classified as cases with refractive astigmatism if the average cylinder power in their two eyes was at least 1.00 diopter and as controls otherwise. Genome-wide association analysis was carried out for each cohort separately using logistic regression. Meta-analysis was conducted using a fixed effects model. In the older European group the most strongly associated marker was downstream of the neurexin-1 (NRXN1) gene (rs1401327, P = 3.92E−8). No other region reached genome-wide significance, and association signals were lower for the younger European group and Asian group. In the meta-analysis of all cohorts, no marker reached genome-wide significance: The most strongly associated regions were, NRXN1 (rs1401327, P = 2.93E−07), TOX (rs7823467, P = 3.47E−07) and LINC00340 (rs12212674, P = 1.49E−06). For 34 markers identified in prior GWAS for spherical equivalent refractive error, the beta coefficients for genotype versus spherical equivalent, and genotype versus refractive astigmatism, were highly correlated (r = −0.59, P = 2.10E−04). This work revealed no consistent or strong genetic signals for refractive astigmatism; however, the TOX gene region previously identified in GWAS for spherical equivalent refractive error was the second most strongly associated region. Analysis of additional markers provided evidence supporting widespread genetic co-susceptibility for spherical and astigmatic refractive errors.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_359,

title = {Environmental immune disruptors, inflammation and cancer risk.},

author = {Thompson PA and Khatami M and Baglole CJ and Sun J and Harris S and Moon EY and Al-Mulla F and Al-Temaimi R and Brown D and Colacci A and Mondello C and Raju J and Ryan E and Woodrick J and Scovassi AI and Singh N and Vaccari M and Roy R and Forte S and Memeo L and Salem HK and Amedei A and Hamid RA and Lowe L and Guarnieri T and Bisson WH},

url = {https://academic.oup.com/carcin/article/36/Suppl_1/S232/316570},

doi = {10.1093/carcin/bgv038},

year  = {2015},

date = {2015-02-21},

urldate = {2015-02-21},

journal = {Carcinogenesis},

volume = {36},

number = {Suppl. 1},

pages = {S232-253},

abstract = {An emerging area in environmental toxicology is the role that chemicals and chemical mixtures have on the cells of the human immune system. This is an important area of research that has been most widely pursued in relation to autoimmune diseases and allergy/asthma as opposed to cancer causation. This is despite the well-recognized role that innate and adaptive immunity play as essential factors in tumorigenesis. Here, we review the role that the innate immune cells of inflammatory responses play in tumorigenesis. Focus is placed on the molecules and pathways that have been mechanistically linked with tumor-associated inflammation. Within the context of chemically induced disturbances in immune function as co-factors in carcinogenesis, the evidence linking environmental toxicant exposures with perturbation in the balance between pro- and anti-inflammatory responses is reviewed. Reported effects of bisphenol A, atrazine, phthalates and other common toxicants on molecular and cellular targets involved in tumor-associated inflammation (e.g. cyclooxygenase/prostaglandin E2, nuclear factor kappa B, nitric oxide synthesis, cytokines and chemokines) are presented as example chemically mediated target molecule perturbations relevant to cancer. Commentary on areas of additional research including the need for innovation and integration of systems biology approaches to the study of environmental exposures and cancer causation are presented. The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_363,

title = {Gallic acid exerts a protective or an anti-proliferative effect on glioma T98G cells via dose-dependent epigenetic regulation mediated by miRNAs.},

author = {Paolini A and Curti V and Pasi F and Mazzini G and Nano R and Capelli E},

url = {https://www.spandidos-publications.com/ijo/46/4/1491},

doi = {10.3892/ijo.2015.2864},

year  = {2015},

date = {2015-02-20},

journal = {International Journal of Oncology},

volume = {46},

number = {4},

pages = {1491-1497},

abstract = {Glioblastoma multiforme (GBM) is the most malignant primary brain tumor in adulthood, characterized by very high recurrence. Following the limited results for conventional therapies, novel therapeutic agents are under investigation. Among the putative new molecules, gallic acid (GA) represents a promising new anticancer drug. The anticancer effect of this drug has been based on its antioxidant effects. The aim of the present study was to investigate the toxic effects of GA on the T98G human glioblastoma cell line and its capacity to modulate the expression of microRNAs targeting the genes involved in tumor growth and invasion. Cytotoxicity, clonogenic ability and cell migration after GA treatment were tested. Moreover, the expression of miRNAs that target genes for antioxidant mitochondrial enzymes (mir-17-3p), p-21 protein (mir-21-5p) and ATM (mir-421-5p) was determined by qRT-PCR. The results confirmed in the T98G cells the anti-proliferative effect of GA reported for other glioma cell lines and showed that the miRNA expression changes depending on GA concentrations. Different GA concentrations can determine a protective or a toxic effect on tumor cells. Thus, the key for GA to induce a specific anticancer action is to use an optimal concentration that avoids these twin effects.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_385,

title = {New light in flavin autofluorescence.},

author = {Croce AC and Bottiroli G},

url = {https://www.ejh.it/index.php/ejh/article/view/2576},

doi = {10.4081/ejh.2015.2576},

year  = {2015},

date = {2015-02-20},

journal = {European Journal of Histochemistry },

volume = {59},

number = {4},

pages = {2576},

abstract = {Our attention was captured by the interesting debate on the identification of lipofuscins, lipofuscin-like lipopigments, or flavins as the responsible for intracellular autofluorescence (AF) detected in epithelial cancer stem cells when exciting at 480-490 nm. Evidence was provided leading to ascribe AF emission to flavins accumulating in cytoplasmic structures, bounded to membranes and bearing ATP-dependent ABCG2 transporters. Flavins were then proposed as an intrinsic AF biomarker of cancer stem cells, with advantageous implications on cell invasiveness and chemoresistance investigations. It is however worth recalling the huge amount of literature on flavins and NAD(P)H as AF biomarkers of cell energetic metabolism and redox state, an aspect that should not be overlooked in the renewed course to extend the potential of flavins as AF biomarkers, entailing also a recent proposal of Flavin-based fluorescent proteins as substitutes of Green fluorescent proteins.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_328,

title = {A dual role for beta1 integrin in an in vitro Streptococcus mitis/human gingival fibroblasts co-culture model in response to TEGDMA.},

author = {{Di Nisio C} and {De Colli M} and {di Giacomo V} and Rapino M and {Di Valerio V} and Marconi GD and Gallorini M and {Di Giulio} M and Cataldi A and Zara S},

doi = {10.1111/iej.12379},

year  = {2015},

date = {2015-02-19},

journal = {International Endodontic Journal},

volume = {48},

number = {9},

abstract = {AIM: To evaluate the effect of TEGDMA on human gingival fibroblasts (HGFs) in vitro co-cultured with Streptococcus mitis, focusing on the signalling pathways underlying cell tissue remodelling and inflammatory response processes. METHODOLOGY:β1 integrin expression was evaluated by means of imaging flow cytometry. The Western blot technique was used to investigate the expression of protein kinase C (PKC), extracellular signal-regulated kinase (ERK), matrix metalloproteinase 9 (MMP9) and 3 (MMP3). RT-PCR was performed to quantify nuclear factor-kb subunits (Nf-kb1, ReLa), IkB kinase β (IkBkB), cyclooxygenase II (COX-2) and tumour necrosis factor-α (TNF-α) mRNA levels. Statistical analysis was performed using the analysis of variance (anova). RESULTS:

When HGFs are co-cultured with S. mitis, β1 integrin intensity, phosphorylated PKC (p-PKC), activated ERK (p-ERK), IkBkB mRNA level and MMP9 expression increased (for all molecules P < 0.05 HGFs versus HGFs co-cultured with S. mitis). A higher level of MMP3 in HGFs treated with TEGDMA was recorded (P < 0.05 HGFs versus HGFs exposed to TEGDMA). COX-2 inflammatory factor mRNA level appeared higher in HGFs exposed to 1 mmol L(-1) TEGDMA (P < 0.01 HGFs versus HGFs exposed to TEGDMA), whereas TNF-α gene expression was higher in HGFs co-cultured with S. mitis (P < 0.05 HGFs versus HGFs co-cultured with S. mitis).CONCLUSIONS: beta1 integrin triggered the signalling pathway, transduced by p-PKCα and involving ERK 1 and 2 and MMPs. This pathway resulted in an unbalanced equilibrium in tissue remodelling process, along with inflammatory response when HGFs are exposed to bacteria or biomaterial alone. On the contrary, the TEGDMA/S. mitis combination restored the balance between extracellular matrix deposition and degradation and prevented an inflammatory response. 2014 International Endodontic Journal. Published by John Wiley & Sons Ltd.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_342,

title = {Causes of genome instability: the effect of low dose chemical exposures in modern society.},

author = {Langie SA and Koppen G and Desaulniers D and Al-Mulla F and Al-Temaimi R and Amedei A and Azqueta A and Bisson WH and Brown D and Brunborg G and Charles AK and Chen T and Colacci A and Darroudi F and Forte S and Gonzalez L and Hamid RA and Knudsen LE and Leyns L and {Lopez de Cerain Salsamendi A} and Memeo L and Mondello C and Mothersill C and Olsen AK and Pavanello S and Raju J and Rojas E and Roy R and Ryan E and Ostrosky-Wegman P and Salem HK and Scovassi AI and Singh N and Vaccari M and {Van Schooten FJ} and Valverde M and Woodrick J and Zhang L and van Larebeke N and Kirsch-Volders M and Collins AR},

url = {https://academic.oup.com/carcin/article/36/Suppl_1/S61/311923},

doi = {10.1093/carcin/bgv031},

year  = {2015},

date = {2015-02-19},

urldate = {2015-02-19},

journal = {Carcinogenesis},

volume = {36},

number = {Suppl. 1},

pages = {S61-88},

abstract = {Genome instability is a prerequisite for the development of cancer. It occurs when genome maintenance systems fail to safeguard the genome's integrity, whether as a consequence of inherited defects or induced via exposure to environmental agents (chemicals, biological agents and radiation). Thus, genome instability can be defined as an enhanced tendency for the genome to acquire mutations; ranging from changes to the nucleotide sequence to chromosomal gain, rearrangements or loss. This review raises the hypothesis that in addition to known human carcinogens, exposure to low dose of other chemicals present in our modern society could contribute to carcinogenesis by indirectly affecting genome stability. The selected chemicals with their mechanisms of action proposed to indirectly contribute to genome instability are: heavy metals (DNA repair, epigenetic modification, DNA damage signaling, telomere length), acrylamide (DNA repair, chromosome segregation), bisphenol A (epigenetic modification, DNA damage signaling, mitochondrial function, chromosome segregation), benomyl (chromosome segregation), quinones (epigenetic modification) and nano-sized particles (epigenetic pathways, mitochondrial function, chromosome segregation, telomere length). The purpose of this review is to describe the crucial aspects of genome instability, to outline the ways in which environmental chemicals can affect this cancer hallmark and to identify candidate chemicals for further study. The overall aim is to make scientists aware of the increasing need to unravel the underlying mechanisms via which chemicals at low doses can induce genome instability and thus promote carcinogenesis.The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_372,

title = {Human nuclear ARGONAUTE 2 interacts in vivo only with small RNAs and not with DNA.},

author = {Gioia U and {d'Adda di Fagagna F}},

url = {https://www.tandfonline.com/doi/full/10.1080/15384101.2015.1044171},

doi = {10.1080/15384101.2015.1044171},

year  = {2015},

date = {2015-02-19},

journal = {Cell Cycle},

volume = {14},

number = {13},

pages = {2001-2002},

abstract = {Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety 'Mode of Action' framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology. The Author 2015. Published by Oxford University Press.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_327,

title = {A DDB2 mutant protein unable to interact with PCNA promotes cell cycle progression of human transformed embryonic kidney cells.},

author = {Perucca P and Sommatis S and Mocchi R and Prosperi E and Stivala LA and Cazzalini O},

url = {https://www.tandfonline.com/doi/full/10.1080/15384101.2015.1120921},

doi = {10.1080/15384101.2015.1120921},

year  = {2015},

date = {2015-02-18},

journal = {Cell Cycle},

volume = {14},

number = {24},

pages = {3920-3928},

abstract = {DNA damage binding protein 2 (DDB2) is a protein involved in the early step of DNA damage recognition of the nucleotide excision repair (NER) process. Recently, it has been suggested that DDB2 may play a role in DNA replication, based on its ability to promote cell proliferation. We have previously shown that DDB2 binds PCNA during NER, but also in the absence of DNA damage; however, whether and how this interaction influences cell proliferation is not known. In this study, we have addressed this question by using HEK293 cell clones stably expressing DDB2(Wt) protein, or a mutant form (DDB2(Mut)) unable to interact with PCNA. We report that overexpression of the DDB2(Mut) protein provides a proliferative advantage over the wild type form, by influencing cell cycle progression. In particular, an increase in the number of S-phase cells, together with a reduction in p21(CDKN1A) protein level, and a shorter cell cycle length, has been observed in the DDB2(Mut) cells. These results suggest that DDB2 influences cell cycle progression thanks to its interaction with PCNA.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_339,

title = {Autophagy in acute leukemias: A double-edged sword with important therapeutic implications},

author = {Evangelisti C and Evangelisti C and Chiarini F and Lonetti A and Buontempo F and Neri LM and McCubrey JA and Martelli AM},

url = {https://www.sciencedirect.com/science/article/pii/S0167488914003486?via%3Dihub},

doi = {10.1016/j.bbamcr.2014.09.023},

year  = {2015},

date = {2015-02-18},

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

volume = {1853},

number = {1},

pages = {14-26},

abstract = {Macroautophagy, usually referred to as autophagy, is a degradative pathway wherein cytoplasmatic components such as aggregated/misfolded proteins and organelles are engulfed within double-membrane vesicles (autophagosomes) and then delivered to lysosomes for degradation. Autophagy plays an important role in the regulation of numerous physiological functions, including hematopoiesis, through elimination of aggregated/misfolded proteins, and damaged/superfluous organelles. The catabolic products of autophagy (amino acids, fatty acids, nucleotides) are released into the cytosol from autophagolysosomes and recycled into bio-energetic pathways. Therefore, autophagy allows cells to survive starvation and other unfavorable conditions, including hypoxia, heat shock, and microbial pathogens. Nevertheless, depending upon the cell context and functional status, autophagy can also serve as a death mechanism. The cohort of proteins that constitute the autophagy machinery function in a complex, multistep biochemical pathway which has been partially identified over the past decade. Dysregulation of autophagy may contribute to the development of several disorders, including acute leukemias. In this kind of hematologic malignancies, autophagy can either act as a chemo-resistance mechanism or have tumor suppressive functions, depending on the context. Therefore, strategies exploiting autophagy, either for activating or inhibiting it, could find a broad application for innovative treatment of acute leukemias and could significantly contribute to improved clinical outcomes. These aspects are discussed here after a brief introduction to the autophagic molecular machinery and its roles in hematopoiesis.Copyright  2014 Elsevier B.V. All rights reserved.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_404,

title = {RNA-processing proteins regulate Mec1/ATR activation by promoting generation of RPA-coated ssDNA.},

author = {Manfrini N and Trovesi C and Wery M and Martina M and Cesena D and Descrimes M and Morillon A and {d'Adda di Fagagna F} and Longhese MP},

url = {https://www.embopress.org/doi/full/10.15252/embr.201439458},

doi = {10.15252/embr.201439458},

year  = {2015},

date = {2015-02-18},

journal = {Embo Reports},

volume = {16},

number = {2},

pages = {221-231},

abstract = {Eukaryotic cells respond to DNA double-strand breaks (DSBs) by activating a checkpoint that depends on the protein kinases Tel1/ATM and Mec1/ATR. Mec1/ATR is activated by RPA-coated single-stranded DNA (ssDNA), which arises upon nucleolytic degradation (resection) of the DSB. Emerging evidences indicate that RNA-processing factors play critical, yet poorly understood, roles in genomic stability. Here, we provide evidence that the Saccharomyces cerevisiae RNA decay factors Xrn1, Rrp6 and Trf4 regulate Mec1/ATR activation by promoting generation of RPA-coated ssDNA. The lack of Xrn1 inhibits ssDNA generation at the DSB by preventing the loading of the MRX complex. By contrast, DSB resection is not affected in the absence of Rrp6 or Trf4, but their lack impairs the recruitment of RPA, and therefore of Mec1, to the DSB. Rrp6 and Trf4 inactivation affects neither Rad51/Rad52 association nor DSB repair by homologous recombination (HR), suggesting that full Mec1 activation requires higher amount of RPA-coated ssDNA than HR-mediated repair. Noteworthy, deep transcriptome analyses do not identify common misregulated gene expression that could explain the observed phenotypes. Our results provide a novel link between RNA processing and genome stability. 2014 The Authors.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_329,

title = {A novel X-linked trichothiodystrophy associated with a nonsense mutation in RNF113A.},

author = {Corbett MA and Dudding-Byth T and Crock PA and Botta E and Christie LM and Nardo T and Caligiuri G and Hobson L and Boyle J and Mansour A and Friend KL and Crawford J and Jackson G and Vandeleur L and Hackett A and Tarpey P and Stratton MR and Turner G and Gécz J and Field M},

url = {https://jmg.bmj.com/content/52/4/269.long},

doi = {10.1136/jmedgenet-2014-102418},

year  = {2015},

date = {2015-02-17},

journal = {Journal of Medical Genetics},

volume = {52},

number = {4},

pages = {269-274},

abstract = {Trichothiodystrophy (TTD) is a group of rare autosomal recessive disorders that variably affect a wide range of organs derived from the neuroectoderm. The key diagnostic feature is sparse, brittle, sulfur deficient hair that has a 'tiger-tail' banding pattern under polarising light microscopy. PATIENTS AND METHODS: We describe two male cousins affected by TTD associated with microcephaly, profound intellectual disability, sparse brittle hair, aged appearance, short stature, facial dysmorphism, seizures, an immunoglobulin deficiency, multiple endocrine abnormalities, cerebellar hypoplasia and partial absence of the corpus callosum, in the absence of cellular photosensitivity and ichthyosis. Obligate female carriers showed 100% skewed X-chromosome inactivation. Linkage analysis and Sanger sequencing of 737 X-chromosome exons and whole exome sequencing was used to find the responsible gene and mutation. RESULTS: Linkage analysis localised the disease allele to a 7.75 Mb interval from Xq23-q25. We identified a nonsense mutation in the highly conserved RNF113A gene (c.901 C>T, p.Q301*). The mutation segregated with the disease in the family and was not observed in over 100,000 control X chromosomes. The mutation markedly reduced RNF113A protein expression in extracts from lymphoblastoid cell lines derived from the affected individuals. CONCLUSIONS: The association of RNF113A mutation with non-photosensitive TTD identifies a new locus for these disorders on the X chromosome. The extended phenotype within this family includes panhypopituitarism, cutis marmorata and congenital short oesophagus. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_331,

title = {An Association Rule Mining Approach to Discover lncRNAs Expression Patterns in Cancer Datasets.},

author = {Cremaschi P and Carriero R and Astrologo S and Colì C and Lisa A and Parolo S and Bione S},

url = {10.1155/2015/146250},

doi = {10.1155/2015/146250},

year  = {2015},

date = {2015-02-14},

journal = {Biomed Research International},

volume = {2015},

pages = {146250},

abstract = {In the past few years, the role of long noncoding RNAs (lncRNAs) in tumor development and progression has been disclosed although their mechanisms of action remain to be elucidated. An important contribution to the comprehension of lncRNAs biology in cancer could be obtained through the integrated analysis of multiple expression datasets. However, the growing availability of public datasets requires new data mining techniques to integrate and describe relationship among data. In this perspective, we explored the powerness of the Association Rule Mining (ARM) approach in gene expression data analysis. By the ARM method, we performed a meta-analysis of cancer-related microarray data which allowed us to identify and characterize a set of ten lncRNAs simultaneously altered in different brain tumor datasets. The expression profiles of the ten lncRNAs appeared to be sufficient to distinguish between cancer and normal tissues. A further characterization of this lncRNAs signature through a comodulation expression analysis suggested that biological processes specific of the nervous system could be compromised.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_340,

title = {Biology of the cell cycle inhibitor p21CDKN1A: molecular mechanisms and relevance in chemical toxicology.},

author = {Dutto I and Tillhon M and Cazzalini O and Stivala LA and Prosperi E},

url = {https://link.springer.com/article/10.1007/s00204-014-1430-4},

doi = { 10.1007/s00204-014-1430-4},

year  = {2015},

date = {2015-02-14},

journal = {Archives of Toxicology},

volume = {89},

pages = {155–178},

abstract = {The cell cycle inhibitor p21(CDKN1A) is a protein playing multiple roles not only in the DNA damage response, but also in many cellular processes during unperturbed cell growth. The main, well-known function of p21 is to arrest cell cycle progression by inhibiting the activity of cyclin-dependent kinases. In addition, p21 is involved in the regulation of transcription, apoptosis, DNA repair, as well as cell motility. However, p21 appears to a have a dual-face behavior because, in addition to its tumor suppressor functions, it may act as an oncogene, depending on the cell type and on the cellular localization. As a biomarker of the cell response to different toxic stimuli, p21 expression and functions have been analyzed in an impressive number of studies investigating the activity of several types of chemicals, in order to determine their possible harmful effects on human cells. Here, we review these studies in order to highlight the different roles p21 may play in the cell response to chemical exposure and to better evaluate the information provided by this biomarker.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_325,

title = {A basal level of DNA damage and telomere deprotection increases the sensitivity of cancer cells to G-quadruplex interactive compounds.},

author = {Salvati E and Rizzo A and Iachettini S and Zizza P and Cingolani C and D'Angelo C and Porru M and Mondello C and Aiello A and Farsetti A and Gilson E and Leonetti C and Biroccio A},

url = {https://academic.oup.com/nar/article/43/3/1759/2411627},

doi = {10.1093/nar/gkv006},

year  = {2015},

date = {2015-02-13},

journal = {Nucleic Acids Research},

volume = {43},

number = {3},

pages = {1759-1769},

abstract = {Here, with the aim of obtaining insight into the intriguing selectivity of G-quadruplex (G4) ligands toward cancer compared to normal cells, a genetically controlled system of progressive transformation in human BJ fibroblasts was analyzed. Among the different comparative evaluations, we found a progressive increase of DNA damage response (DDR) markers throughout the genome from normal toward immortalized and transformed cells. More interestingly, sensitivity to G4 ligands strongly correlated with the presence of a basal level of DNA damage, including at the telomeres, where the chromosome ends were exposed to the DDR without concurrent induction of DNA repair activity, as revealed by the lack of 53BP1 recruitment and telomere aberrations. The link between telomere uncapping and the response to G4 stabilization was directly assessed by showing that a partial TRF2 depletion, causing a basal level of telomere localized DDR, rendered telomerized fibroblasts prone to G4-induced telomere damage and anti-proliferative defects. Taken together these data strongly indicate that the presence of a basal level of telomere-associated DDR is a determinant of susceptibility to G4 stabilization. The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_337,

title = {Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead.},

author = {{Goodson WH 3d} and Lowe L and Carpenter DO and Gilbertson M and Manaf Ali A and {Lopez de Cerain Salsamendi A} and Lasfar A and Carnero A and Azqueta A and Amedei A and Charles AK and Collins AR and Ward A and Salzberg AC and Colacci A and Olsen AK and Berg A and Barclay BJ and Zhou BP and Blanco-Aparicio C and Baglole CJ and Dong C and Mondello C and Hsu CW and Naus CC and Yedjou C and Curran CS and Laird DW and Koch DC and Carlin DJ and Felsher DW and Roy D and Brown DG and Ratovitski E and Ryan EP and Corsini E and Rojas E and Moon EY and Laconi E and Marongiu F and Al-Mulla F and Chiaradonna F and Darroudi F and Martin FL and Van Schooten FJ and Goldberg GS and Wagemaker G and Nangami G and Calaf GM and Williams G and Wolf GT and Koppen G and Brunborg G and Kim Lyerly H and Krishnan H and Ab Hamid H and Yasaei H and Sone H and Kondoh H and Salem HK and Hsu HY and Park HH and Koturbash I and Miousse IR and Scovassi AI and Klaunig JE and Vondráček J and Raju J and Roman J and Wise JP Sr and Whitfield JR and Woodrick J and Christopher JA and Ochieng J and Martinez-Leal JF and Weisz J and Kravchenko J and Sun J and Prudhomme KR and Narayanan KB and Cohen-Solal KA and Moorwood K and Gonzalez L and Soucek L and Jian L and D'Abronzo LS and Lin LT and Li L and Gulliver L and McCawley LJ and Memeo L and Vermeulen L and Leyns L and Zhang L and Valverde M and Khatami M and Romano MF and Chapellier M and Williams MA and Wade M and Manjili MH and Lleonart M and Xia M and Gonzalez MJ and Karamouzis MV and Kirsch-Volders M and Vaccari M and Kuemmerle NB and Singh N and Cruickshanks N and Kleinstreuer N and van Larebeke N and Ahmed N and Ogunkua O and Krishnakumar PK and Vadgama P and Marignani PA and Ghosh PM and Ostrosky-Wegman P and Thompson P and Dent P and Heneberg P and Darbre P and Sing Leung P and Nangia-Makker P and Cheng QS and Robey RB and Al-Temaimi R and Roy R and Andrade-Vieira R and Sinha RK and Mehta R and Vento R and Di Fiore R and Ponce-Cusi R and Dornetshuber-Fleiss R and Nahta R and Castellino RC and Palorini R and Abd Hamid R and Langie SA and Eltom S and Brooks SA and Ryeom S and Wise SS and Bay SN and Harris SA and Papagerakis S and Romano S and Pavanello S and Eriksson S and Forte S and Casey SC and Luanpitpong S and Lee TJ and Otsuki T and Chen T and Massfelder T and Sanderson T and Guarnieri T and Hultman T and Dormoy V and Odero-Marah V and Sabbisetti V and Maguer-Satta V and Rathmell WK and Engström W and Decker WK and Bisson WH and Rojanasakul Y and Luqmani Y and Chen Z and Hu Z},

url = {https://academic.oup.com/carcin/article/36/Suppl_1/S254/316933},

doi = {10.1093/carcin/bgv039},

year  = {2015},

date = {2015-02-13},

journal = {Carcinogenesis},

volume = {36},

number = {Suppl. 1},

pages = {S254-96},

abstract = {Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety 'Mode of Action' framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology. The Author 2015. Published by Oxford University Press.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_354,

title = {Disruptive chemicals, senescence and immortality.},

author = {Carnero A and Blanco-Aparicio C and Kondoh H and Lleonart ME and Martinez-Leal JF and Mondello C and Scovassi AI and Bisson WH and Amedei A and Roy R and Woodrick J and Colacci A and Vaccari M and Raju J and Al-Mulla F and Al-Temaimi R and Salem HK and Memeo L and Forte S and Singh N and Hamid RA and Ryan EP and Brown DG and Wise JP Sr and Wise SS and Yasaei H},

url = {https://academic.oup.com/carcin/article/36/Suppl_1/S19/311053},

doi = {10.1093/carcin/bgv029},

year  = {2015},

date = {2015-02-13},

urldate = {2015-02-13},

journal = {Carcinogenesis},

volume = {36},

number = {Suppl. 1},

pages = {S19-37},

abstract = {Carcinogenesis is thought to be a multistep process, with clonal evolution playing a central role in the process. Clonal evolution involves the repeated 'selection and succession' of rare variant cells that acquire a growth advantage over the remaining cell population through the acquisition of 'driver mutations' enabling a selective advantage in a particular micro-environment. Clonal selection is the driving force behind tumorigenesis and possesses three basic requirements: (i) effective competitive proliferation of the variant clone when compared with its neighboring cells, (ii) acquisition of an indefinite capacity for self-renewal, and (iii) establishment of sufficiently high levels of genetic and epigenetic variability to permit the emergence of rare variants. However, several questions regarding the process of clonal evolution remain. Which cellular processes initiate carcinogenesis in the first place? To what extent are environmental carcinogens responsible for the initiation of clonal evolution? What are the roles of genotoxic and non-genotoxic carcinogens in carcinogenesis? What are the underlying mechanisms responsible for chemical carcinogen-induced cellular immortality? Here, we explore the possible mechanisms of cellular immortalization, the contribution of immortalization to tumorigenesis and the mechanisms by which chemical carcinogens may contribute to these processes. The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_358,

title = {Effect of new berberine derivatives on colon cancer cells.},

author = {Guamán Ortiz LM and Croce AL and Aredia F and Sapienza S and Fiorillo G and Syeda TM and Buzzetti F and Lombardi P and Scovassi AI},

url = {https://academic.oup.com/abbs/article/47/10/824/1754528},

doi = {10.1093/abbs/gmv077},

year  = {2015},

date = {2015-02-13},

journal = {Acta Biochimica et Biophysica Sinica},

volume = {47},

number = {10},

pages = {824-33},

abstract = {The natural alkaloid berberine has been recently described as a promising anticancer drug. In order to improve its efficacy and bioavailability, several derivatives have been designed and synthesized and found to be even more potent than the lead compound. Among the series of berberine derivatives we have produced, five compounds were identified to be able to heavily affect the proliferation of human HCT116 and SW613-B3 colon carcinoma cell lines. Remarkably, these active compounds exhibit high fluorescence emission property and ability to induce autophagy. The Author 2015. Published by ABBS Editorial Office in association with Oxford University Press on behalf of the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_373,

title = {Improving clinical trial design for Duchenne muscular dystrophy.},

author = {Merlini L and Sabatelli P},

url = {https://bmcneurol.biomedcentral.com/articles/10.1186/s12883-015-0408-z},

doi = {10.1186/s12883-015-0408-z},

year  = {2015},

date = {2015-02-13},

journal = {BMC Neurology},

volume = {15},

pages = {153},

abstract = {BACKGROUND: Currently, the most promising therapies for Duchenne muscular dystrophy (DMD) are exon skipping and stop codon read-through, two strategies aimed at restoring the expression of dystrophin. A phase 3 clinical trial with drisapersen, a drug designed to induce exon 51-skipping, has failed to show significant improvement of the primary outcome measure, the six-minute walk test. DISCUSSION: Here, we review some key points that should be considered when designing clinical trials for these new therapies. First, younger patients have more functional abilities and more muscle fibers to preserve than older patients and therefore are better subjects for trials designed to demonstrate the success of new treatments. Second, the inclusion of patients on corticosteroids both in the treatment and placebo groups is of concern because the positive effect of corticosteroids might mask the effect of the treatment being tested. Additionally, the reasonable expectation from these therapies is the slowing of disease progression rather than improvement. Therefore, the appropriate clinical endpoints are the prolongation of the ability to stand from the floor, climb stairs, and walk, not an increase in muscle strength or function. Hence, the time frames for the detection of new dystrophin, which occurs within months, and the ability to demonstrate a slowing of disease progression, which requires years, are strikingly different. Finally, placebo-controlled trials are difficult to manage if years of blindness are required to demonstrate a slowing of disease progression. Thus, accelerated/conditional approval for new therapies should be based on surrogate biochemical outcomes: the demonstration of de novo dystrophin production and of its beneficial effect on the functional recovery of muscle fiber. These data suggest that clinical trials for DMD patients must be adapted to the particular characteristics of the disease in order to demonstrate the expected positive effect of new treatments.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_324,

title = {3D silicon microstructures: a new tool for evaluating biological aggressiveness of tumour cells.},

author = {Mazzini G and Carpignano F and Surdo S and Aredia F and Torchio M and Erba E and Danova M and Scovassi AI and Barillaro G and Merlo S},

url = {https://ieeexplore.ieee.org/document/7239627},

doi = {10.1109/TNB.2015.2476351},

year  = {2015},

date = {2015-02-12},

urldate = {2015-02-12},

journal = {IEEE Trans Nanobioscience },

volume = {14},

number = {7},

pages = {797-805},

abstract = {In this work, silicon micromachined structures (SMS), consisting of arrays of 3-μm-thick silicon walls separated by 50-μm-deep, 5-μm-wide gaps, were applied to investigate the behavior of eight tumor cell lines, with different origins and biological aggressiveness, in a three-dimensional (3D) microenvironment. Several cell culture experiments were performed on 3D-SMS and cells grown on silicon were stained for fluorescence microscopy analyses. Most of the tumor cells lines recognized in the literature as highly aggressive (OVCAR-5, A375, MDA-MB-231, and RPMI-7951) exhibited a great ability to enter and colonize the narrow deep gaps of the SMS, whereas less aggressive cell lines (OVCAR-3, Capan-1, MCF7, and NCI-H2126) demonstrated less penetration capability and tended to remain on top of the SMS. Quantitative image analyses of several fluorescence microscopy fields of silicon samples were performed for automatic cell recognition and count, in order to quantify the fraction of cells inside the gaps, with respect to the total number of cells in the examined field. Our results show that higher fractions of cells in the gaps are obtained with more aggressive cell lines, thus supporting in a quantitative way the observation that the behavior of tumor cells on the 3D-SMS depends on their aggressiveness level.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_332,

title = {An integrated optofluidic device for single-cell sorting driven by mechanical properties.},

author = {Yang T and Paiè P and Nava G and Bragheri F and {Martinez Vazquez R} and Minzioni P and Veglione M and Di Tano M and Mondello C and Osellame R and Cristiani I},

url = {https://pubs.rsc.org/en/content/articlelanding/2015/LC/C4LC01496K#!divAbstract},

doi = {10.1039/c4lc01496k},

year  = {2015},

date = {2015-02-12},

journal = {Lab on a Chip},

volume = {15},

number = {5},

pages = {1262-1266},

abstract = {We present a novel optofluidic device for real-time sorting on the basis of cell mechanical properties, measured by optical stretching. The whole mechanism, based on optical forces, does not hamper the viability of the tested cells, which can be used for further analysis. The device effectiveness is demonstrated by extracting a sample population enriched with highly metastatic cells from a heterogeneous cell mixture.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_334,

title = {An overview of new translational, clinical and therapeutic perspectives in laminopathies and other nuclear envelope-related diseases.},

author = {{De Sandre-Giovannoli A} and Levy N Ben Yaou R and Leturcq F Lattanzi G and Bonne G},

url = {https://ojrd.biomedcentral.com/articles/10.1186/1750-1172-10-S2-I1#citeas},

doi = {10.1186/1750-1172-10-S2-I1},

year  = {2015},

date = {2015-02-12},

journal = {Orphanet Journal of Rare Diseases},

volume = {10},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_341,

title = {Carvacrol codrugs: a new approach in the antimicrobial plan.},

author = {Cacciatore I and Di Giulio M and Fornasari E and Di Stefano A and Cerasa LS and Marinelli L and Turkez H and Di Campli E and Di Bartolomeo S and Robuffo I and Cellini L},

url = {https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0120937},

doi = {10.1371/journal.pone.0120937},

year  = {2015},

date = {2015-02-12},

journal = {Plos One},

volume = {10},

number = {4},

pages = {e0120937},

abstract = {OBJECTIVE: The increasing prevalence of antibiotic-resistant bacterial infections led to identify alternative strategies for a novel therapeutic approach. In this study, we synthesized ten carvacrol codrugs - obtained linking the carvacrol hydroxyl group to the carboxyl moiety of sulphur-containing amino acids via an ester bond - to develop novel compounds with improved antimicrobial and antibiofilm activities and reduced toxicity respect to carvacrol alone. METHOD: All carvacrol codrugs were screened against a representative panel of Gram positive (S. aureus and S. epidermidis), Gram negative (E. coli and P. aeruginosa) bacterial strains and C. albicans, using broth microdilution assays. FINDINGS: Results showed that carvacrol codrug 4 possesses the most notable enhancement in the anti-bacterial activity displaying MIC and MBC values equal to 2.5 mg/mL for all bacterial strains, except for P. aeruginosa ATCC 9027 (MIC and MBC values equal to 5 mg/mL and 10 mg/mL, respectively). All carvacrol codrugs 1-10 revealed good antifungal activity against C. albicans ATCC 10231. The cytotoxicity assay showed that the novel carvacrol codrugs did not produce human blood hemolysis at their MIC values except for codrugs 8 and 9. In particular, deepened experiments performed on carvacrol codrug 4 showed an interesting antimicrobial effect on the mature biofilm produced by E. coli ATCC 8739, respect to the carvacrol alone. The antimicrobial effects of carvacrol codrug 4 were also analyzed by TEM evidencing morphological modifications in S. aureus, E. coli, and C. albican CONCLUSION: The current study presents an insight into the use of codrug strategy for developing carvacrol derivatives with antibacterial and antibiofilm potentials, and reduced cytotoxicity.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}