@article{Incollu2026-ce,

title = {Allelic variation in the ATP7B gene promoter. Implications for  phenotype variability, neurodegeneration and Pt resistance in  tumor diseases},

author = {Simona Incollu and Isadora Asunis and Stefania Satta and Salvatore Savasta and Georgios Loudianos},

year  = {2026},

date = {2026-03-01},

urldate = {2026-03-01},

journal = {J. Hum. Genet.},

publisher = {Springer Science and Business Media LLC},

abstract = {Wilson's disease (WD) is a rare genetic disorder of copper 

 transport due to mutations in the ATP7B gene. This results in 

 copper overload and tissue damage that is most evident in the 

 liver and brain. Over 1000 pathogenic mutations have been found 

 in WD patients, and of these, mutations within the ATP7B coding 

 region predominate. In this study, we perform functional 

 analyses of 7 rare sequence variations in the promoter region of 

 the ATP7B gene. We performed dual luciferase reporter assays in 

 HepG2 and SH-SY5Y cell lines under basal conditions and after 

 the addition of 10 $mu$M or 40 $mu$M concentrations of CuSO4. 

 The results showed that promoter activity varied both according 

 to the haplotype and the cell line used. Our results suggest a 

 potential role of promoter polymorphisms in the variation of 

 ATP7B gene expression with probable implications in copper 

 accumulation in the organism and consequent phenotype variation 

 in WD. In addition, given the association of copper 

 concentration and ATP7B expression in the brain, promoter 

 polymorphisms could act as susceptibility determinants of 

 neurodegeneration in the most common late-onset nervous system 

 diseases. Finally, promoter involvement in ATP7B overexpression 

 and platinum resistance presents new mechanisms of great 

 importance that need to be better understood. Further 

 experimental and clinical studies are necessary to further 

 explore the role of the ATP7B promoter in copper and platinum 

 management. These studies will offer new insights for the 

 development of molecular therapies for brain degenerative and 

 tumor diseases.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Wu2026-wl,

title = {The interplay of sleep characteristics with health factors and 

 gut microbiome},

author = {Jiafei Wu and Sergio Andreu-Sánchez and Haoran Peng and Ranko Gacesa and Milla Brand ao Gois and Siobhan Brushett and Rinse Weersma and Daoming Wang and Alexander Kurilshikov and Alexandra Zhernakova and Jingyuan Fu and Daria V Zhernakova},

year  = {2026},

date = {2026-02-01},

journal = {Nat. Commun.},

volume = {17},

number = {1},

publisher = {Springer Science and Business Media LLC},

abstract = {Emerging evidence suggests a bidirectional relationship between 

 sleep and the gut microbiome. In this study, we explore the 

 associations of sleep characteristics with lifestyle factors and 

 gut microbiome composition in 6941 participants from the 

 Lifelines Dutch Microbiome Project. We show that lower alpha 

 diversity is associated with poorer sleep quality, later 

 chronotype, and greater social jet lag, while beta diversity is 

 linked to both sleep quality and social jet lag. Of the 137 

 bacterial species associated with sleep, 35.6% are validated in 

 an independent cohort. Mediation analyses indicate that, while 

 changes in species abundance are largely a consequence of sleep 

 behavior, certain species may mediate diet's influence on sleep. 

 For example, we find that Clostridia species UC5_1_1E11 and 

 SGB14844 mediate the effect of coffee intake on social jet lag. 

 These findings highlight the intricate relationship between 

 diet, the gut microbiome, and sleep, suggesting the potential 

 for microbiome-targeted interventions to improve sleep health.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Gacem2026-sl,

title = {In silico screening and preclinical validation identify bavisant 

 as a therapeutic candidate for multiple sclerosis},

author = {Nadjet Gacem and Svetlana Bezukladova and Farina Windener and Tala Karam and Linda Ottoboni and Elena Brambilla and Francesca Ruffini and Karthik Soman and Beatriz Garcia-Diaz and Marion J F Levy and Qiao-Ling Cui and Alessia Formato and Cyrille Deboux and Jeremy Chazot and Radmila Panic and Stefanie Albrecht and Elif Nur Yilmaz and Raquel Guerrero González and Ivano Eberini and Stefania Olla and Alberto Bresciani and Norbert Goebels and Frauke Zipp and Cristina Agresti and Jack Antel and Anne Baron-Van Evercooren and Tanja Kuhlmann and Sergio E Baranzini and Paola Panina-Bordignon and Brahim Nait-Oumesmar and Gianvito Martino},

year  = {2026},

date = {2026-01-01},

journal = {Sci. Transl. Med.},

volume = {18},

number = {833},

pages = {eads0633},

abstract = {Current treatments for multiple sclerosis (MS) are insufficient 

 to delay the neurodegenerative process that is the main cause of 

 disability progression in patients with MS. Therapeutics aimed at 

 supporting myelin regeneration and neuroprotection are thus a 

 major unmet medical need for the progressive forms of MS. To 

 address this, we developed a strategy combining in silico 

 screening of more than 1500 repurposed compounds with a 

 validation pipeline of models, encompassing rodent and human in 

 vitro assays as well as mouse models of 

 demyelination/remyelination. From the initial library, 273 drugs 

 were prioritized in silico on the basis of the predicted effects 

 on myelination and neuroprotection, and among them, 160 were 

 potentially nontoxic. We identified 32 molecules that exerted a 

 promyelinating and a neuroprotective action on rodent and human 

 oligodendroglia and neurons. Our data identified classes of 

 compounds with potentially distinct mechanisms of action that may 

 foster remyelination and neuroprotection. The therapeutic 

 activity of one selected drug, the histamine receptor H3 

 antagonist bavisant, was further validated in mouse models of 

 demyelination and axonal injury reproducing some key pathological 

 features occurring in MS. Our in vivo studies demonstrated that 

 bavisant promoted remyelination and neuroprotection when 

 administered to LPC-treated, cuprizone-fed, or MOG-induced EAE 

 mice, as well as in a human oligodendroglia chimeric mouse model 

 of demyelination/remyelination. These findings provide 

 proof-of-concept validation for bavisant as a candidate for 

 neuroprotective clinical trials in MS.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Ferrando2026-fp,

title = {Aging in women - The microbiome perspective},

author = {Maria Laura Ferrando and Fabio Busonero and Francesca Crobu and Serena Sanna},

year  = {2026},

date = {2026-01-01},

urldate = {2026-01-01},

journal = {Ägeing Res. Rev.},

volume = {113},

number = {102950},

pages = {102950},

publisher = {Elsevier BV},

abstract = {Menopause is a hallmark of women's aging and is frequently 

 portrayed as a medical issue. It also encompasses social and 

 biological aspects often neglected and not well-understood, 

 leaving women with insufficient support and attention. With the 

 decline in estrogen levels, starting years before menopause is 

 fully established, women experience various physical symptoms, 

 and the risk of many age-related diseases increases sharply soon 

 after these hormonal changes occur. Notably, these hormonal 

 shifts also significantly impact the vaginal and gut 

 microbiomes, contributing to dysbiosis and influencing the onset 

 and progression of several diseases. Here, we examined the 

 complex and dynamic relationship among aging, menopause, and 

 microbiome changes with a particular focus on the vaginal and 

 gut ecosystems. Emerging research highlights diet as a potential 

 modulator for maintaining microbiome health during menopause. A 

 deeper understanding of microbiome changes across life stages 

 suggests the potential for microbiome-targeted strategies to 

 support well-aging in women.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Olla2025-lv,

title = {Phage display selection and in silico characterization of 

 peptides as potential GroEL modulators},

author = {Stefania Ölla and Stella Garcia Colombarolli and Chiara Siguri and Davide Murrau and Alberto" Vitali},

year  = {2025},

date = {2025-12-01},

journal = {Pharmaceutics},

volume = {18},

number = {1},

pages = {46},

publisher = {MDPI AG},

abstract = {Background/Objectives. Antibiotic resistance is an escalating 

 global health concern, highlighting the need for innovative 

 antibacterial strategies beyond traditional drugs. GroEL, a 

 highly conserved bacterial chaperonin essential for protein 

 folding and stress tolerance, represents a promising but 

 underexplored therapeutic target. This study aimed to identify 

 short peptides capable of binding GroEL monomers and potentially 

 altering their function, with the long-term goal of disrupting 

 bacterial survival mechanisms. Methods. A phage display 

 screening of a 12-mer peptide library was performed against 

 purified GroEL monomers, yielding five candidate peptides 

 (G1-G5). Their interactions with GroEL were analyzed through 

 molecular docking and molecular dynamics simulations using 

 three-dimensional GroEL structures (1MNF, 1XCK, 8S32). Stability 

 of binding and interaction profiles were assessed through 

 molecular dynamics-based analyses and MM/GBSA free energy 

 calculations. Results. Peptides G4 and G5 displayed the most 

 stable and energetically favorable interactions, with G4-8S32 

 showing the strongest binding (-116.68 kcal/mol). These peptides 

 localized near inter-subunit interfaces, suggesting potential 

 interference with GroEL oligomerization or allosteric 

 transitions, which are critical for its biological function. 

 Conclusions. Our findings demonstrate that short peptides can 

 stably bind GroEL and potentially modulate its activity. 

 Peptides G4 and G5 represent at our knowledge the first 

 promising scaffolds for developing a novel class of 

 peptide-based antibacterial agents targeting conserved 

 chaperonin systems. This work introduces a new avenue that 

 warrants further experimental validation.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Olla2025-or,

title = {Substituted 2-pyrrolinone compounds as inhibitors of B-cell 

 activating factor (BAFF) for autoimmune diseases treatment},

author = {Stefania Ölla and Maria Laura Idda and Manila Deiana and Valeria Lodde and Giuseppe Delogu and Antonio Cristian Caria and Matteo Floris and Francesco" Cucca},

year  = {2025},

date = {2025-11-01},

journal = {Life Sci.},

volume = {380},

number = {123938},

pages = {123938},

publisher = {Elsevier BV},

abstract = {B-cell activating factor (BAFF) is a cytokine that plays a 

 critical role in the proliferation and differentiation of B 

 cells. We have previously demonstrated that its inherited 

 overexpression is associated with increased circulating B cell 

 and immunoglobulin levels, correlating with increased risk of 

 multiple sclerosis and systemic lupus erythematosus. These 

 findings suggest that enhanced BAFF expression may be involved 

 in the causal biology of these disorders, thus supporting the 

 rationale for therapeutic inhibition of this cytokine. However, 

 to date, no small-molecule modulator capable of inhibiting BAFF 

 is available. We therefore employed a virtual screening approach 

 to analyze a library of 275,561 small molecules, followed by in 

 vitro validation of 218 selected compounds with potential to 

 disrupt the interaction between BAFF and its receptor BAFFR. Our 

 results identified two promising small molecules, C45 and C145, 

 belonging to the substituted 2-pyrrolinone family, which 

 effectively inhibited BAFF activity. These compounds warrant 

 further investigation as potential therapeutic agents for 

 BAFF-driven autoimmune diseases.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Vinerbi2025-yc,

title = {Lactobacillus iners dominates the vaginal microbiota of healthy 

 Italian women of reproductive age},

author = {E Vinerbi and F Chillotti and A Maschio and S Lenarduzzi and S Camarda and F Crobu and D V Zhernakova and V Lo Faro and G Beltrame Vriz and S Incollu and J Spreckels and N Kuzub and A Kadric and R Gacesa and A Zhernakova and F De Seta and D Mazz`a and F Busonero and M L Ferrando and G Girotto and S Sanna},

year  = {2025},

date = {2025-11-01},

journal = {mSystems},

number = {e00983-25},

pages = {e0098325},

publisher = {Ämerican Society for Microbiology"},

abstract = {Large sex hormonal fluctuations are thought to influence vaginal 

 microbiota, but little is known about the impact of small, 

 physiological variations. Here, we tracked changes in vaginal 

 microbiota during four key menstrual cycle phases in 61 healthy, 

 naturally menstruating Italian women from the Women4Health 

 cohort. The microbiota, characterized using a high-depth 16S 

 rRNA amplicon sequencing approach covering four hypervariable 

 regions, was primarily composed of Lactobacillus species, with 

 Lactobacillus iners being the most abundant (average relative 

 abundance: 40%) and the most prevalent (prevalence: 98%). 

 Individual microbiota were generally stable, but beta diversity was higher during the follicular phase (P = 0.007). Only 11 

 women exhibited compositional shifts, mostly occurring between 

 the follicular and ovulatory phases. Finally, using linear mixed 

 models, we assessed the association between taxa relative 

 abundance and five sex hormones along the menstrual cycle. Among 

 these, 17-beta estradiol showed the largest number of 

 significant associations, linking its increase to a decrease in 

 the relative abundance of taxa that are more common after 

 menopause. Our study highlights specific features of the Italian 

 population and points to the resilience of the vaginal 

 microbiota to physiological hormonal changes. Noteworthy, the 

 observed high abundance of L. iners contrasts with previous 

 studies in European populations, challenging its proposed 

 pathogenic role and suggesting distinct microbiota profiles 

 within Europe.IMPORTANCEThe vaginal microbiota plays an 

 important role in women's health, yet we know little about how 

 it responds to normal hormonal fluctuations. In this study, we 

 followed 61 healthy Italian women over a natural menstrual cycle 

 to explore microbiota changes across different hormonal phases. 

 We found that Lactobacillus iners was the most common species, 

 unlike previous findings in Northern Europe, suggesting 

 population-specific patterns. The common hypothesis that L. 

 iners is invariably linked with poor health is called into 

 question by our findings. They emphasize the importance of 

 considering population context and hormonal status when 

 assessing vaginal health. The vaginal microbiota was generally 

 stable, with only a few changes observed between the follicular 

 and ovulatory phases. When evaluating the association between 

 five sex hormones and taxa abundances, we found that 17-beta 

 estradiol levels had the largest number of significant 

 associations. These highlight an association between increased 

 levels of 17-beta estradiol and increased relative abundance of 

 rare bacterial taxa rather than dominant species like 

 Lactobacillus. Our findings help define what constitutes a 

 ``healthy microbiota'' in generally healthy Italian women of 

 reproductive age and may inform future strategies for diagnosing 

 or preventing women's health conditions.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Mingoia2025-rn,

title = {A novel intronic variant in the KH3 domain of HNRNPK leads  to a mild form of Au-Kline syndrome},

author = {Maura Mingoia and Alessandra Meloni and Silvia Sedda and Sanaa Choufani and Isadora Asunis and Giorgia Gemma and Antonio Ammendola and Arteen Torabi-Marashi and Eleonora Venere and Gabriella Maria Squeo and Vincenzo Rallo and Maria Giuseppina Marini and Paolo Moi and Salvatore Savasta and Rosanna Weksberg and Giuseppe Merla and Andrea Angius},

year  = {2025},

date = {2025-11-01},

urldate = {2025-11-01},

journal = {Clin. Genet.},

volume = {108},

number = {5},

pages = {576--581},

publisher = {Wiley},

abstract = {Despite the massive adoption of sequencing technologies, 

 disease-specific diagnosis remains challenging, particularly for 

 genes with highly homologous pseudogenes like HNRNPK. Pathogenic 

 HNRNPK variants cause Au-Kline syndrome (AKS), a 

 neurodevelopmental disorder with malformations and distinctive 

 facial features. We validated a novel de novo HNRNPK intronic 

 variant (c.1192-3 C>A, p.Leu398ValfsTer21) in a patient 

 previously misdiagnosed with Kabuki Syndrome (KS). By combining 

 sequencing, in vitro splicing assays, molecular modelling, and 

 protein function analysis, we characterised the molecular 

 defect. A unique DNA methylation (DNAm) signature was recently 

 identified in AKS, with missense variants showing an 

 intermediate DNAm pattern, suggesting an epi-genotype-phenotype 

 correlation linked to milder clinical features. The DNAm 

 signature is a valuable tool for variant interpretation, 

 especially in unclear AKS cases. We demonstrate that two 

 independent approaches-functional characterisation and DNAm 

 evaluation-confirmed a partial loss of HNRNPK function and 

 validated an AKS diagnosis with a mild phenotype. Our findings 

 highlight that a multidisciplinary approach integrating genomic 

 and epigenomic analyses with functional studies and clinical 

 assessment significantly improves rare disease diagnosis.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Cacciola2025-ix,

title = {The Anti-Angiogenic Effect of Cynara cardunculus L. subsp. 

 cardunculus Waste Product},

author = {Anna Cacciola and Valeria DÁngelo and Federica De Gaetano and Antonella Fais and Maria Paola German`o and Valentina Masala and Stefania Olla and Venerando Pistar`a and Rosanna Stancanelli and Carlo Ignazio Giovanni Tuberoso and Cinzia Anna Ventura},

year  = {2025},

date = {2025-07-01},

journal = {Foods},

volume = {14},

number = {15},

pages = {2656},

publisher = {MDPI AG},

abstract = {Cynara cardunculus L. subsp. cardunculus (Cynara cardunculus L. 

 var. sylvestris (Lam.) Fiori), the wild cardoon, is known for 

 its culinary applications and potential health benefits. Due to 

 this, and given the growing interest in circular economies, 

 deepening our under-standing of the effects of wild cardoon leaf 

 waste on angiogenesis and collagenase activity represents a 

 valuable opportunity to valorise agricultural byproducts as 

 health-promoting ingredients. In this study, the waste product 

 of wild cardoon leaves was extracted to examine its chemical 

 composition and biological activities. Analytical techniques 

 identified several bioactive compounds, including flavonoids, 

 hydroxycinnamic acids such as dicaffeoyl-succinoylquinic acids, 

 and luteolin-7-O-rutinoside. In vivo tests in zebrafish embryos 

 and the chick chorioallantoic membrane demonstrated 

 dose-dependent antiangiogenic effects, particularly enhanced by 

 the complexation with hydroxypropyl-$beta$-cyclodextrin 

 (HP-$beta$-CD). Considering the link between angiogenesis and 

 collagenase, the potential effects of the extract on collagenase 

 activity was investigated. The extract alone inhibited 

 collagenase with an IC50 value comparable to that of the 

 standard inhibitor while its complexed form exhibited a 4.5-fold 

 greater inhibitory activity. A molecular docking study examined 

 the interaction between the main compounds and collagenase. In 

 conclusion, wild cardoon leaves can represent a valuable source 

 of bioactive compounds. This study demonstrated that the 

 complexation of the extract with cyclodextrin determines an 

 increase in its biological activity.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Simbula2025-nd,

title = {Drugs repurposing of molecules modulating human delta globin 

 gene expression via a model of transgenic foetal liver cells: 

 Implications for beta-hemoglobinopathy therapeutics},

author = {Michela Simbula and Maria Francesca Manchinu and Stefania Olla and Michela Congiu and Simona Vaccargiu and Cristian Antonio Caria and Daniela Poddie and Maria Serafina Ristaldi},

year  = {2025},

date = {2025-04-01},

journal = {Biomolecules},

volume = {15},

number = {4},

pages = {565},

publisher = {MDPI AG},

abstract = {Beta-hemoglobinopathies such as beta-thalassemia and sickle cell 

 disease are severe genetic blood disorders affecting the beta 

 globin chain of haemoglobin A ($alpha$2$beta$2). Activation of 

 delta globin, the non-alpha globin of HbA2 ($alpha$2$delta$2), 

 could represent a possible approach to improve the clinical 

 severity of these pathologies. Notably, the therapeutic 

 potential of delta globin has been demonstrated in previous 

 studies using a mouse model of beta-thalassemia and sickle cell 

 disease. The present study evaluated delta globin gene 

 activation by small molecules in erythroid cells isolated from 

 transgenic murine foetal liver. A screening of 119 molecules, 

 selected for their potential in drug repurposing, was performed 

 without prior selection based on specific pathways of interest. 

 Three candidates-Nexturastat, Stattic and Palbociclib-were found 

 to have high efficacy on delta globin expression. Palbociclib 

 also proved effective in increasing gamma globin expression. All 

 of these compounds have pharmacokinetic profiles that are 

 beneficial for clinical application, providing potential inducer 

 agents of HbA2 that could have therapeutic effects in the 

 treatment of beta-hemoglobinopathies.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Floris2024-lf,

title = {Biological potential of Asphodelus microcarpus extracts: 

 $A$-glucosidase and antibiofilm activities in vitro},

author = {Sonia Floris and Francesca Pintus and Antonella Fais and Benedetta Era and Nicola Raho and Chiara Siguri and Germano Orr`u and Sara Fais and Carlo Ignazio Giovanni Tuberoso and Stefania Olla and Amalia Di Petrillo},

year  = {2024},

date = {2024-10-01},

journal = {Molecules},

volume = {29},

number = {21},

pages = {5063},

publisher = {MDPI AG},

abstract = {Type 2 diabetes (T2D), characterized by insulin resistance and 

 $beta$-cell dysfunction, requires continuous advancements in 

 management strategies, particularly in controlling postprandial 

 hyperglycemia to prevent complications. Current antidiabetics, 

 which have $alpha$-amylase and $alpha$-glucosidase inhibitory 

 activities, have side effects, prompting the search for better 

 alternatives. In addition, diabetes patients are particularly 

 vulnerable to yeast infections because an unusual sugar 

 concentration promotes the growth of Candida spp. in areas like 

 the mouth and genitalia. Asphodelus microcarpus contains 

 bioactive flavonoids with potential enzyme inhibitory 

 properties. This study investigates $alpha$-amylase and 

 $alpha$-glucosidase inhibitory activities and antioxidant and 

 antimycotic capacity of ethanolic extracts from different parts 

 of A. microcarpus. Results show that extracts significantly 

 inhibit $alpha$-glucosidase, with the IC50 value being up to 25 

 times higher than for acarbose, while exerting low 

 $alpha$-amylase activity. The extracts also demonstrated strong 

 antioxidant properties and low cytotoxicity. The presence of 

 phenolic compounds is likely responsible for the observed 

 biological activities. Molecular docking analysis of 11 selected 

 compounds identified emodin and luteolin as significant 

 inhibitors of $alpha$-glucosidase. Additionally, the extracts 

 demonstrated significant antibiofilm action against an MDR 

 strain of Candida albicans. These findings suggest that A. 

 microcarpus is a promising source of natural compounds for T2D 

 management.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Caballero-Oteyza2024-rg,

title = {OTULIN-related conditions: Report of a new case and review of 

 the literature using GenIA},

author = {Andrés Caballero-Oteyza and Laura Crisponi and Xiao P Peng and Hongying Wang and Pavla Mrovecova and Stefania Olla and Chiara Siguri and Farida Marnissi and Zineb Jouhadi and Ivona Aksentijevich and Bodo Grimbacher and Michele Proietti},

year  = {2024},

date = {2024-08-01},

journal = {Clin. Immunol.},

volume = {265},

number = {110292},

pages = {110292},

publisher = {Elsevier BV},

abstract = {ÖTULIN encodes an eponymous linear deubiquitinase (DUB) 

 essential for controlling inflammation as a negative regulator 

 of the canonical NF-$kappa$B signaling pathway via the 

 regulation of M1-Ub dynamics. Biallelic loss-of-function (LOF) 

 mutations in OTULIN cause an autosomal recessive condition named 

 Otulin-Related Autoinflammatory Syndrome (ORAS), also known as 

 Otulipenia or AutoInflammation, Panniculitis, and Dermatosis 

 Syndrome (AIPDS). Monoallelic OTULIN LOF, also known as OTULIN 

 Haploinsufficiency (OHI) or Immunodeficiency 107 (IMD107), has 

 been linked to an incompletely penetrant, dominantly inherited 

 susceptibility to invasive Staphylococcal infections. At the 

 same time, a recent novel ORAS-like inflammatory syndrome was 

 described in association with a heterozygous missense mutation 

 that appears to exert dominant negative (DN) effects. In this 

 manuscript, we report the identification of a novel homozygous 

 missense mutation, c.595 T > A; p.(Trp199Arg), in a Moroccan 

 infant with an ORAS phenotype and provide experimental evidence 

 for its pathogenicity. We go on to systematically review the 

 literature for OTULIN-associated conditions by using the GenIA 

 database (www.geniadb.net) to collect, extract and harmonize all 

 clinical, laboratory and functional data for published patients 

 and variants. Our comprehensive synthesis of genotypic, 

 phenotypic, and mechanistic data enables a more in-depth view of 

 the diverse mechanisms and pathways by which the OTULIN 

 pathogenic variants may lead to human immune disease. This 

 review may help variant classification activities and inform 

 future variant evaluation, as well as the development of 

 diagnostic and management guidelines. It also identifies current 

 knowledge gaps and raises additional questions warranting future 

 investigation."},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Piperni2024-av,

title = {Intestinal Blastocystis is linked to healthier diets and more  favorable cardiometabolic outcomes in 56,989 individuals from 32  countries},

author = {Elisa Piperni and Long H Nguyen and Paolo Manghi and Hanseul Kim and Edoardo Pasolli and Sergio Andreu-Sánchez and Alberto Arr`e and Kate M Bermingham and Aitor Blanco-M'iguez and Serena Manara and Mireia Valles-Colomer and Elco Bakker and Fabio Busonero and Richard Davies and Edoardo Fiorillo and Francesca Giordano and George Hadjigeorgiou and Emily R Leeming and Monia Lobina and Marco Masala and Andrea Maschio and Lauren J McIver and Mauro Pala and Maristella Pitzalis and Jonathan Wolf and Jingyuan Fu and Alexandra Zhernakova and Simone M Cacci`o and Francesco Cucca and Sarah E Berry and Danilo Ercolini and Andrew T Chan and Curtis Huttenhower and Tim D Spector and Nicola Segata and Francesco Asnicar},

doi = {10.1016/j.cell.2024.06.018},

year  = {2024},

date = {2024-08-01},

urldate = {2024-08-01},

journal = {Cell},

volume = {187},

number = {17},

pages = {4554--4570.e18},

publisher = {Elsevier BV},

abstract = {Diet impacts human health, influencing body adiposity and the 

 risk of developing cardiometabolic diseases. The gut microbiome 

 is a key player in the diet-health axis, but while its bacterial 

 fraction is widely studied, the role of micro-eukaryotes, 

 including Blastocystis, is underexplored. We performed a 

 global-scale analysis on 56,989 metagenomes and showed that 

 human Blastocystis exhibits distinct prevalence patterns linked 

 to geography, lifestyle, and dietary habits. Blastocystis 

 presence defined a specific bacterial signature and was 

 positively associated with more favorable cardiometabolic 

 profiles and negatively with obesity (p < 1e-16) and disorders 

 linked to altered gut ecology (p < 1e-8). In a diet intervention 

 study involving 1,124 individuals, improvements in dietary 

 quality were linked to weight loss and increases in Blastocystis prevalence (p = 0.003) and abundance (p < 1e-7). Our findings 

 suggest a potentially beneficial role for Blastocystis, which 

 may help explain personalized host responses to diet and 

 downstream disease etiopathogenesis.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Piperni2024-ph,

title = {Intestinal Blastocystis is linked to healthier diets and more  favorable cardiometabolic outcomes in 56,989 individuals from 32  countries},

author = {Elisa Piperni and Long H Nguyen and Paolo Manghi and Hanseul Kim and Edoardo Pasolli and Sergio Andreu-Sánchez and Alberto Arr`e and Kate M Bermingham and Aitor Blanco-M'iguez and Serena Manara and Mireia Valles-Colomer and Elco Bakker and Fabio Busonero and Richard Davies and Edoardo Fiorillo and Francesca Giordano and George Hadjigeorgiou and Emily R Leeming and Monia Lobina and Marco Masala and Andrea Maschio and Lauren J McIver and Mauro Pala and Maristella Pitzalis and Jonathan Wolf and Jingyuan Fu and Alexandra Zhernakova and Simone M Cacci`o and Francesco Cucca and Sarah E Berry and Danilo Ercolini and Andrew T Chan and Curtis Huttenhower and Tim D Spector and Nicola Segata and Francesco Asnicar},

doi = {10.1016/j.cell.2024.06.018},

year  = {2024},

date = {2024-08-01},

urldate = {2024-08-01},

journal = {Cell},

volume = {187},

number = {17},

pages = {4554--4570.e18},

publisher = {Elsevier BV},

abstract = {Diet impacts human health, influencing body adiposity and the 

 risk of developing cardiometabolic diseases. The gut microbiome 

 is a key player in the diet-health axis, but while its bacterial 

 fraction is widely studied, the role of micro-eukaryotes, 

 including Blastocystis, is underexplored. We performed a 

 global-scale analysis on 56,989 metagenomes and showed that 

 human Blastocystis exhibits distinct prevalence patterns linked 

 to geography, lifestyle, and dietary habits. Blastocystis 

 presence defined a specific bacterial signature and was 

 positively associated with more favorable cardiometabolic 

 profiles and negatively with obesity (p < 1e-16) and disorders 

 linked to altered gut ecology (p < 1e-8). In a diet intervention 

 study involving 1,124 individuals, improvements in dietary 

 quality were linked to weight loss and increases in Blastocystis prevalence (p = 0.003) and abundance (p < 1e-7). Our findings 

 suggest a potentially beneficial role for Blastocystis, which 

 may help explain personalized host responses to diet and 

 downstream disease etiopathogenesis.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Serra2024-ps,

title = {Ä large-scale screening identified in USH2A gene the P3272L 

 founder pathogenic variant explaining familial Usher syndrome in 

 Sardinia, Italy"},

author = {Rita Serra and Vincenzo Rallo and Maristella Steri and Stefania Olla and Maria Grazia Piras and Michele Marongiu and Myriam Gorospe and David Schlessinger and Antonio Pinna and Edoardo Fiorillo and Francesco Cucca and Andrea Angius},

year  = {2024},

date = {2024-07-01},

journal = {BMC Ophthalmol.},

volume = {24},

number = {1},

pages = {306},

publisher = {Springer Science and Business Media LLC},

abstract = {BACKGROUND: Usher syndrome (USH) encompasses a group of 

 disorders characterized by congenital sensorineural hearing loss 

 (SNHL) and retinitis pigmentosa (RP). We described the clinical 

 findings, natural history, and molecular analyses of USH 

 patients identified during a large-scale screening to identify 

 quantitative traits related to ocular disorders in the SardiNIA 

 project cohort. METHODS: We identified 3 USH-affected families 

 out of a cohort of 6,148 healthy subjects. 9 subjects presented 

 a pathological phenotype, with SNHL and RP. All patients and 

 their family members underwent a complete ophthalmic examination 

 including best-corrected visual acuity, slit-lamp biomicroscopy, 

 fundoscopy, fundus autofluorescence, spectral-domain optical 

 coherence tomography, and electrophysiological testing. 

 Audiological evaluation was performed with a clinical 

 audiometer. Genotyping was performed using several arrays 

 integrated with whole genome sequence data providing 

 approximately 22 million markers equally distributed for each 

 subject analyzed. Molecular diagnostics focused on analysis of 

 the following candidate genes: MYO7A, USH1C, CDH23, PCDH15, 

 USH1G, CIB2, USH2A, GPR98, DFNB31, CLRN1, and PDZD7. RESULTS: A 

 single missense causal variant in USH2A gene was identified in 

 homozygous status in all patients and in heterozygous status in 

 unaffected parents. The presence of multiple homozygous patients 

 with the same phenotypic severity of the syndromic form suggests 

 that the Sardinian USH phenotype is the result of a founder 

 effect on a specific pathogenic variant related haplotype. The 

 frequency of heterozygotes in general Sardinian population is 

 1.89. Additionally, to provide new insights into the structure 

 of usherin and the pathological mechanisms caused by small 

 pathogenic in-frame variants, like p.Pro3272Leu, molecular 

 dynamics simulations of native and mutant protein-protein and 

 protein-ligand complexes were performed that predicted a 

 destabilization of the protein with a decrease in the free 

 energy change. CONCLUSIONS: Our results suggest that our 

 approach is effective for the genetic diagnosis of USH. Based on 

 the heterozygous frequency, targeted screening of this variant 

 in the general population and in families at risk or with 

 familial USH can be suggested. This can lead to more accurate 

 molecular diagnosis, better genetic counseling, and improved 

 molecular epidemiology data that are critical for future 

 intervention plans. TRIAL REGISTRATION: We did not perform any 

 health-related interventions for the participants.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Di_Petrillo2024-ac,

title = {Exploring Asphodelus microcarpus as a source of xanthine oxidase 

 inhibitors: Insights from in silico and in vitro studies},

author = {Amalia Di Petrillo and Chiara Siguri and Giovanna L Delogu and Antonella Fais and Benedetta Era and Sonia Floris and Francesca Pintus and Amit Kumar and Massimo Claudio Fantini and Stefania Olla},

year  = {2024},

date = {2024-07-01},

journal = {Chem. Biol. Interact.},

volume = {397},

number = {111087},

pages = {111087},

publisher = {Elsevier BV},

abstract = {Xanthine oxidase (XO) plays a critical role in purine 

 catabolism, catalyzing the conversion of hypoxanthine to 

 xanthine and xanthine to uric acid, contributing to superoxide 

 anion production. This process is implicated in various human 

 diseases, particularly gout. Traditional XO inhibitors, such as 

 allopurinol and febuxostat, while effective, may present side 

 effects. Our study focuses on Asphodelus microcarpus, a plant 

 renowned for traditional anti-inflammatory uses. Recent 

 investigations into its phenolic-rich flowers, notably abundant 

 in luteolin derivatives, reveal its potential as a natural 

 source of XO inhibitors. In the present research, XO inhibition 

 by an ethanolic flowers extract from A. microcarpus is reported. 

 In silico docking studies have highlighted luteolin derivatives 

 as potential XO inhibitors, and molecular dynamics support that 

 luteolin 7-O-glucoside has the highest binding stability 

 compared to other compounds and controls. In vitro studies 

 confirm that luteolin 7-O-glucoside inhibits XO more effectively 

 than the standard inhibitor allopurinol, with an IC50 value of 

 4.8 $mu$g/mL compared to 11.5 $mu$g/mL, respectively. These 

 findings underscore the potential therapeutic significance of A. 

 microcarpus in managing conditions related to XO activity. The 

 research contributes valuable insights into the health-promoting 

 properties of A. microcarpus and its potential application in 

 natural medicine, presenting a promising avenue for further 

 exploration in disease management.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Atzeni2024-tj,

title = {A novel affordable and reliable framework for accurate detection  and comprehensive analysis of somatic mutations in cancer},

author = {Rossano Atzeni and Matteo Massidda and Enrico Pieroni and Vincenzo Rallo and Massimo Pisu and Andrea Angius},

year  = {2024},

date = {2024-07-01},

urldate = {2024-07-01},

journal = {Int. J. Mol. Sci.},

volume = {25},

number = {15},

pages = {8044},

publisher = {MDPI AG},

abstract = {Äccurate detection and analysis of somatic variants in cancer 

 involve multiple third-party tools with complex dependencies and 

 configurations, leading to laborious, error-prone, and 

 time-consuming data conversions. This approach lacks accuracy, 

 reproducibility, and portability, limiting clinical application. 

 Musta was developed to address these issues as an end-to-end 

 pipeline for detecting, classifying, and interpreting cancer 

 mutations. Musta is based on a Python command-line tool designed 

 to manage tumor-normal samples for precise somatic mutation 

 analysis. The core is a Snakemake-based workflow that covers all 

 key cancer genomics steps, including variant calling, mutational 

 signature deconvolution, variant annotation, driver gene 

 detection, pathway analysis, and tumor heterogeneity estimation. 

 Musta is easy to install on any system via Docker, with a 

 Makefile handling installation, configuration, and execution, 

 allowing for full or partial pipeline runs. Musta has been 

 validated at the CRS4-NGS Core facility and tested on large 

 datasets from The Cancer Genome Atlas and the Beijing Institute 

 of Genomics. Musta has proven robust and flexible for somatic 

 variant analysis in cancer. It is user-friendly, requiring no 

 specialized programming skills, and enables data processing with 

 a single command line. Its reproducibility ensures consistent 

 results across users following the same protocol."},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Orru2024-ec,

title = {Implications of disease-modifying therapies for multiple  sclerosis on immune cells and response to COVID-19 vaccination},

author = {Valeria Orrù and Valentina Serra and Michele Marongiu and Sandra Lai and Valeria Lodde and Magdalena Zoledziewska and Maristella Steri and Annalisa Loizedda and Monia Lobina and Maria Grazia Piras and Francesca Virdis and Giuseppe Delogu and Maria Giuseppina Marini and Maura Mingoia and Matteo Floris and Marco Masala and M Paola Castelli and Rafaela Mostallino and Jessica Frau and Lorena Lorefice and Gabriele Farina and Marzia Fronza and Daniele Carmagnini and Elisa Carta and Silvy Pilotto and Paola Chessa and Marcella Devoto and Paolo Castiglia and Paolo Solla and Roberto Ignazio Zarbo and Maria Laura Idda and Maristella Pitzalis and Eleonora Cocco and Edoardo Fiorillo and Francesco Cucca},

year  = {2024},

date = {2024-07-01},

urldate = {2024-07-01},

journal = {Front. Immunol.},

volume = {15},

pages = {1416464},

publisher = {Frontiers Media SA},

abstract = {Introduction: Disease-modifying therapies (DMTs) have been shown 

 to improve disease outcomes in multiple sclerosis (MS) patients. 

 They may also impair the immune response to vaccines, including 

 the SARS-CoV-2 vaccine. However, available data on both the 

 intrinsic immune effects of DMTs and their influence on cellular 

 response to the SARS-CoV-2 vaccine are still incomplete. 

 Methods: Here, we evaluated the immune cell effects of 3 DMTs on 

 the response to mRNA SARS-CoV-2 vaccination by comparing MS 

 patients treated with one specific therapy (fingolimod, dimethyl 

 fumarate, or natalizumab) with both healthy controls and 

 untreated patients. We profiled 23 B-cell traits, 57 T-cell 

 traits, and 10 cytokines, both at basal level and after 

 stimulation with a pool of SARS-CoV-2 spike peptides, in 79 MS 

 patients, treated with DMTs or untreated, and 32 healthy 

 controls. Measurements were made before vaccination and at three 

 time points after immunization. Results and Discussion: MS 

 patients treated with fingolimod showed the strongest immune 

 cell dysregulation characterized by a reduction in all measured 

 lymphocyte cell classes; the patients also had increased immune 

 cell activation at baseline, accompanied by reduced specific 

 immune cell response to the SARS-CoV-2 vaccine. Also, anti-spike 

 specific B cells progressively increased over the three time 

 points after vaccination, even when antibodies measured from the 

 same samples instead showed a decline. Our findings demonstrate 

 that repeated booster vaccinations in MS patients are crucial to 

 overcoming the immune cell impairment caused by DMTs and 

 achieving an immune response to the SARS-CoV-2 vaccine 

 comparable to that of healthy controls.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Orru2024-hd,

title = {Implications of disease-modifying therapies for multiple  sclerosis on immune cells and response to COVID-19 vaccination},

author = {Valeria Örr`u and Valentina Serra and Michele Marongiu and Sandra Lai and Valeria Lodde and Magdalena Zoledziewska and Maristella Steri and Annalisa Loizedda and Monia Lobina and Maria Grazia Piras and Francesca Virdis and Giuseppe Delogu and Maria Giuseppina Marini and Maura Mingoia and Matteo Floris and Marco Masala and M Paola Castelli and Rafaela Mostallino and Jessica Frau and Lorena Lorefice and Gabriele Farina and Marzia Fronza and Daniele Carmagnini and Elisa Carta and Silvy Pilotto and Paola Chessa and Marcella Devoto and Paolo Castiglia and Paolo Solla and Roberto Ignazio Zarbo and Maria Laura Idda and Maristella Pitzalis and Eleonora Cocco and Edoardo Fiorillo and Francesco" Cucca},

doi = {10.3389/fimmu.2024.1416464},

year  = {2024},

date = {2024-07-01},

urldate = {2024-07-01},

journal = {Front. Immunol.},

volume = {15},

pages = {1416464},

publisher = {Frontiers Media SA},

abstract = {Introduction: Disease-modifying therapies (DMTs) have been shown 

 to improve disease outcomes in multiple sclerosis (MS) patients. 

 They may also impair the immune response to vaccines, including 

 the SARS-CoV-2 vaccine. However, available data on both the 

 intrinsic immune effects of DMTs and their influence on cellular 

 response to the SARS-CoV-2 vaccine are still incomplete. 

 Methods: Here, we evaluated the immune cell effects of 3 DMTs on 

 the response to mRNA SARS-CoV-2 vaccination by comparing MS 

 patients treated with one specific therapy (fingolimod, dimethyl 

 fumarate, or natalizumab) with both healthy controls and 

 untreated patients. We profiled 23 B-cell traits, 57 T-cell 

 traits, and 10 cytokines, both at basal level and after 

 stimulation with a pool of SARS-CoV-2 spike peptides, in 79 MS 

 patients, treated with DMTs or untreated, and 32 healthy 

 controls. Measurements were made before vaccination and at three 

 time points after immunization. Results and Discussion: MS 

 patients treated with fingolimod showed the strongest immune 

 cell dysregulation characterized by a reduction in all measured 

 lymphocyte cell classes; the patients also had increased immune 

 cell activation at baseline, accompanied by reduced specific 

 immune cell response to the SARS-CoV-2 vaccine. Also, anti-spike 

 specific B cells progressively increased over the three time 

 points after vaccination, even when antibodies measured from the 

 same samples instead showed a decline. Our findings demonstrate 

 that repeated booster vaccinations in MS patients are crucial to 

 overcoming the immune cell impairment caused by DMTs and 

 achieving an immune response to the SARS-CoV-2 vaccine 

 comparable to that of healthy controls.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Serra2024-gb,

title = {A large-scale screening identified in USH2A gene the P3272L  founder pathogenic variant explaining familial Usher syndrome in  Sardinia, Italy},

author = {Rita Serra and Vincenzo Rallo and Maristella Steri and Stefania Olla and Maria Grazia Piras and Michele Marongiu and Myriam Gorospe and David Schlessinger and Antonio Pinna and Edoardo Fiorillo and Francesco Cucca and Andrea Angius},

year  = {2024},

date = {2024-07-01},

urldate = {2024-07-01},

journal = {BMC Ophthalmol.},

volume = {24},

number = {1},

pages = {306},

publisher = {Springer Science and Business Media LLC},

abstract = {BACKGROUND: Usher syndrome (USH) encompasses a group of 

 disorders characterized by congenital sensorineural hearing loss 

 (SNHL) and retinitis pigmentosa (RP). We described the clinical 

 findings, natural history, and molecular analyses of USH 

 patients identified during a large-scale screening to identify 

 quantitative traits related to ocular disorders in the SardiNIA 

 project cohort. METHODS: We identified 3 USH-affected families 

 out of a cohort of 6,148 healthy subjects. 9 subjects presented 

 a pathological phenotype, with SNHL and RP. All patients and 

 their family members underwent a complete ophthalmic examination 

 including best-corrected visual acuity, slit-lamp biomicroscopy, 

 fundoscopy, fundus autofluorescence, spectral-domain optical 

 coherence tomography, and electrophysiological testing. 

 Audiological evaluation was performed with a clinical 

 audiometer. Genotyping was performed using several arrays 

 integrated with whole genome sequence data providing 

 approximately 22 million markers equally distributed for each 

 subject analyzed. Molecular diagnostics focused on analysis of 

 the following candidate genes: MYO7A, USH1C, CDH23, PCDH15, 

 USH1G, CIB2, USH2A, GPR98, DFNB31, CLRN1, and PDZD7. RESULTS: A 

 single missense causal variant in USH2A gene was identified in 

 homozygous status in all patients and in heterozygous status in 

 unaffected parents. The presence of multiple homozygous patients 

 with the same phenotypic severity of the syndromic form suggests 

 that the Sardinian USH phenotype is the result of a founder 

 effect on a specific pathogenic variant related haplotype. The 

 frequency of heterozygotes in general Sardinian population is 

 1.89. Additionally, to provide new insights into the structure 

 of usherin and the pathological mechanisms caused by small 

 pathogenic in-frame variants, like p.Pro3272Leu, molecular 

 dynamics simulations of native and mutant protein-protein and 

 protein-ligand complexes were performed that predicted a 

 destabilization of the protein with a decrease in the free 

 energy change. CONCLUSIONS: Our results suggest that our 

 approach is effective for the genetic diagnosis of USH. Based on 

 the heterozygous frequency, targeted screening of this variant 

 in the general population and in families at risk or with 

 familial USH can be suggested. This can lead to more accurate 

 molecular diagnosis, better genetic counseling, and improved 

 molecular epidemiology data that are critical for future 

 intervention plans. TRIAL REGISTRATION: We did not perform any 

 health-related interventions for the participants.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid38672460,

title = {The Antioxidant Drug Edaravone Binds to the Aryl Hydrocarbon Receptor (AHR) and Promotes the Downstream Signaling Pathway Activation},

author = {C. Veroni and S. Olla and M. S. Brignone and C. Siguri and A. Formato and M. Marra and R. Manzoli and M. C. Macario and E. Ambrosini and E. Moro and C. Agresti},

year  = {2024},

date = {2024-04-04},

journal = {Biomolecules},

volume = {14},

number = {4},

abstract = {A considerable effort has been spent in the past decades to develop targeted therapies for the treatment of demyelinating diseases, such as multiple sclerosis (MS). Among drugs with free radical scavenging activity and oligodendrocyte protecting effects, Edaravone (Radicava) has recently received increasing attention because of being able to enhance remyelination in experimental in vitro and in vivo disease models. While its beneficial effects are greatly supported by experimental evidence, there is a current paucity of information regarding its mechanism of action and main molecular targets. By using high-throughput RNA-seq and biochemical experiments in murine oligodendrocyte progenitors and SH-SY5Y neuroblastoma cells combined with molecular docking and molecular dynamics simulation, we here provide evidence that Edaravone triggers the activation of aryl hydrocarbon receptor (AHR) signaling by eliciting AHR nuclear translocation and the transcriptional-mediated induction of key cytoprotective gene expression. We also show that an Edaravone-dependent AHR signaling transduction occurs in the zebrafish experimental model, associated with a downstream upregulation of the NRF2 signaling pathway. We finally demonstrate that its rapid cytoprotective and antioxidant actions boost increased expression of the promyelinating Olig2 protein as well as of an Olig2:GFP transgene in vivo. We therefore shed light on a still undescribed potential mechanism of action for this drug, providing further support to its therapeutic potential in the context of debilitating demyelinating conditions.},

note = {[PubMed Central:hrefhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2948512PMC2948512] [DOI:hrefhttps://dx.doi.org/10.1371/journal.pone.001312810.1371/journal.pone.0013128] [PubMed:hrefhttps://www.ncbi.nlm.nih.gov/pubmed/2095704620957046]},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Pintori2024-na,

title = {Immune and glial cell alterations in the rat brain after  repeated exposure to the synthetic cannabinoid JWH-018},

author = {Nicholas Pintori and Rafaela Mostallino and Enrica Spano and Valeria Orr`u and Maria Grazia Piras and Maria Paola Castelli and Maria Antonietta De Luca},

doi = {10.1016/j.jneuroim.2024.578325},

year  = {2024},

date = {2024-04-01},

urldate = {2024-04-01},

journal = {J. Neuroimmunol.},

volume = {389},

number = {578325},

pages = {578325},

publisher = {Elsevier BV},

abstract = {The use of synthetic cannabinoid receptor agonists (SCRAs) poses 

 major psychiatric risks. We previously showed that repeated 

 exposure to the prototypical SCRA JWH-018 induces alterations in 

 dopamine (DA) transmission, abnormalities in the emotional 

 state, and glial cell activation in the mesocorticolimbic DA 

 circuits of rats. Despite growing evidence suggesting the 

 relationship between substance use disorders (SUD) and 

 neuroinflammation, little is known about the impact of SCRAs on 

 the neuroimmune system. Here, we investigated whether repeated 

 JWH-018 exposure altered neuroimmune signaling, which could be 

 linked with previously reported central effects. Adult male 

 Sprague-Dawley (SD) rats were exposed to JWH-018 (0.25 mg/kg, 

 i.p.) for fourteen consecutive days, and the expression of 

 cytokines, chemokines, and growth factors was measured seven 

 days after treatment discontinuation in the striatum, cortex, 

 and hippocampus. Moreover, microglial (ionized calcium-binding 

 adaptor molecule 1, IBA-1) and astrocyte (glial fibrillary 

 acidic protein, GFAP) activation markers were evaluated in the 

 caudate-putamen (CPu). Repeated JWH-018 exposure induces a 

 perturbation of neuroimmune signaling specifically in the 

 striatum, as shown by increased levels of cytokines 

 [interleukins (IL) -2, -4, -12p70, -13, interferon (IFN) 

 $gamma$], chemokines [macrophage inflammatory protein (MIP) 

 -1$alpha$, -3$alpha$], and growth factors [macrophage 

 colony-stimulating factor (M-CSF), vascular endothelial growth 

 factor (VEGF)], together with increased IBA-1 and GFAP 

 expression in the CPu. JWH-018 exposure induces persistant brain 

 region-specific immune alterations up to seven days after drug 

 discontinuation, which may contribute to the behavioral and 

 neurochemical dysregulations in striatal areas that play a role 

 in the reward-related processes that are frequently impaired in 

 SUD.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Forabosco2024-jt,

title = {Transcriptome organization of white blood cells through gene  co-expression network analysis in a large RNA-seq dataset},

author = {Paola Forabosco and Mauro Pala and Francesca Crobu and Maria Antonietta Diana and Mara Marongiu and Roberto Cusano and Andrea Angius and Maristella Steri and Valeria Orr`u and David Schlessinger and Edoardo Fiorillo and Marcella Devoto and Francesco Cucca},

doi = {10.3389/fimmu.2024.1350111},

year  = {2024},

date = {2024-04-01},

urldate = {2024-04-01},

journal = {Front. Immunol.},

volume = {15},

pages = {1350111},

abstract = {Gene co-expression network analysis enables identification of 

 biologically meaningful clusters of co-regulated genes (modules) 

 in an unsupervised manner. We present here the largest study 

 conducted thus far of co-expression networks in white blood cells 

 (WBC) based on RNA-seq data from 624 individuals. We identify 41 

 modules, 13 of them related to specific immune-related functions 

 and cell types (e.g. neutrophils, B and T cells, NK cells, and 

 plasmacytoid dendritic cells); we highlight biologically relevant 

 lncRNAs for each annotated module of co-expressed genes. We 

 further characterize with unprecedented resolution the modules in 

 T cell sub-types, through the availability of 95 immune 

 phenotypes obtained by flow cytometry in the same individuals. 

 This study provides novel insights into the transcriptional 

 architecture of human leukocytes, showing how network analysis 

 can advance our understanding of coding and non-coding gene 

 interactions in immune system cells.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Sterzi2024-xo,

title = {Genetic barriers more than environmental associations explain 

 Serratia marcescens population structure},

author = {Lodovico Sterzi and Riccardo Nodari and Federico Di Marco and Maria Laura Ferrando and Francesca Saluzzo and Andrea Spitaleri and Hamed Allahverdi and Stella Papaleo and Simona Panelli and Sara Giordana Rimoldi and Gherard Batisti Biffignandi and Marta Corbella and Annalisa Cavallero and Paola Prati and Claudio Farina and Daniela Maria Cirillo and Gianvincenzo Zuccotti and Claudio Bandi and Francesco Comandatore},

year  = {2024},

date = {2024-04-01},

journal = {Commun. Biol.},

volume = {7},

number = {1},

pages = {468},

abstract = {Bacterial species often comprise well-separated lineages, likely 

 emerged and maintained by genetic isolation and/or ecological 

 divergence. How these two evolutionary actors interact in the 

 shaping of bacterial population structure is currently not fully 

 understood. In this study, we investigate the genetic and 

 ecological drivers underlying the evolution of Serratia 

 marcescens, an opportunistic pathogen with high genomic 

 flexibility and able to colonise diverse environments. 

 Comparative genomic analyses reveal a population structure 

 composed of five deeply-demarcated genetic clusters with open 

 pan-genome but limited inter-cluster gene flow, partially 

 explained by Restriction-Modification (R-M) systems 

 incompatibility. Furthermore, a large-scale research on 

 hundred-thousands metagenomic datasets reveals only a partial 

 habitat separation of the clusters. Globally, two clusters only 

 show a separate gene composition coherent with ecological 

 adaptations. These results suggest that genetic isolation has 

 preceded ecological adaptations in the shaping of the species 

 diversity, an evolutionary scenario coherent with the 

 Evolutionary Extended Synthesis.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{,

title = {Iodinated 4,4’-Bipyridines with Antiproliferative Activity Against Melanoma Cell Lines},

author = {Peluso Paola and Mamane Victor and Spissu Ylenia and Casu Giuseppina and Dessì Alessandro and Dallocchio Roberto and Sechi Barbara and Palmieri Giuseppe and Rozzo Carla. },

url = {https://irgb.cnr.it/chemmedchem-2024-peluso-et-al-2024-2/},

doi = {doi.org/10.1002/cmdc.202300662},

issn = {1860-7187},

year  = {2024},

date = {2024-03-15},

urldate = {2024-03-15},

journal = {Chemical Medicinal Chemistry},

number = {e202300662},

pages = {1-12},

abstract = {In the last decade, biological processes involving halogen bond (HaB) as a leading interaction attracted great interest. Iodinated 4,4’-bipyridines showed interesting properties as HaB donors in solution and in the solid state. This study represents a proof-of-principle exploration aiming to investigate the effectiveness of new iodinated compounds against melanoma cells. The authors investigated on the inhibition activity exerted by seven halogenated 4,4’-bipyridines on malignant melanoma cell proliferation. The 3,3’,5,5’-tetrachloro-2-iodo-4,4’-bipyridine showed significant antiproliferation activity against the A375 cell line, and lower toxicity on BJ fibroblasts. The results suggested that the antiproliferative activity, at molecular level, may be correlated with the electrophilic properties of iodine. Through in silico studies, the stereoelectronic features of possible sites determining the bioactivity were explored. The obtained results confirmed the high potential of iodinated compounds in designing novel anti-melanoma therapeutics strategies considering the utilization of iodinated 4,4’-bipyridines as templates to design new promising HaB-enabled inhibitors of MM cell proliferation, paving the way for a new perspective in this field.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Busonero2024-ks,

title = {The Women4Health cohort: a unique cohort to study 

 women-specific mechanisms of cardio-metabolic regulation},

author = {Fabio Busonero and Stefania Lenarduzzi and Francesca Crobu and Roberta Marie Gentile and Andrea Carta and Francesco Cracco and Andrea Maschio and Silvia Camarda and Michele Marongiu and Daniela Zanetti and Claudio Conversano and Giovanni Di Lorenzo and Daniela Mazz`a and Francesco De Seta and Giorgia Girotto and Serena Sanna},

year  = {2024},

date = {2024-03-01},

journal = {Eur. Heart J. Open},

volume = {4},

number = {2},

pages = {öeae012"},

publisher = {Öxford University Press (OUP)"},

abstract = {Äims: Epidemiological research has shown relevant differences 

 between sexes in clinical manifestations, severity, and 

 progression of cardiovascular and metabolic disorders. To date, 

 the mechanisms underlying these differences remain unknown. 

 Given the rising incidence of such diseases, gender-specific 

 research on established and emerging risk factors, such as 

 dysfunction of glycaemic and/or lipid metabolism, of sex 

 hormones and of gut microbiome, is of paramount importance. The 

 relationships between sex hormones, gut microbiome, and host 

 glycaemic and/or lipid metabolism are largely unknown even in 

 the homoeostasis status. Yet this knowledge gap would be pivotal 

 to pinpoint to key mechanisms that are likely to be disrupted in 

 disease context. Methods and results: Here we present the 

 Women4Health (W4H) cohort, a unique cohort comprising up to 300 

 healthy women followed up during a natural menstrual cycle, set 

 up with the primary goal to investigate the combined role of sex 

 hormones and gut microbiota variations in regulating host lipid 

 and glucose metabolism during homoeostasis, using a multi-omics 

 strategy. Additionally, the W4H cohort will take into 

 consideration another ecosystem that is unique to women, the 

 vaginal microbiome, investigating its interaction with gut 

 microbiome and exploring-for the first time-its role in 

 cardiometabolic disorders. Conclusion: The W4H cohort study lays 

 a foundation for improving current knowledge of women-specific 

 mechanisms in cardiometabolic regulation. It aspires to 

 transform insights on host-microbiota interactions into 

 prevention and therapeutic approaches for personalized health 

 care."},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Busonero2024-et,

title = {The Women4Health cohort: a unique cohort to study 

 women-specific mechanisms of cardio-metabolic regulation},

author = {Fabio Busonero and Stefania Lenarduzzi and Francesca Crobu and Roberta Marie Gentile and Andrea Carta and Francesco Cracco and Andrea Maschio and Silvia Camarda and Michele Marongiu and Daniela Zanetti and Claudio Conversano and Giovanni Di Lorenzo and Daniela Mazz`a and Francesco De Seta and Giorgia Girotto and Serena Sanna},

year  = {2024},

date = {2024-03-01},

journal = {Eur. Heart J. Open},

volume = {4},

number = {2},

pages = {öeae012"},

publisher = {Öxford University Press (OUP)"},

abstract = {Äims: Epidemiological research has shown relevant differences 

 between sexes in clinical manifestations, severity, and 

 progression of cardiovascular and metabolic disorders. To date, 

 the mechanisms underlying these differences remain unknown. 

 Given the rising incidence of such diseases, gender-specific 

 research on established and emerging risk factors, such as 

 dysfunction of glycaemic and/or lipid metabolism, of sex 

 hormones and of gut microbiome, is of paramount importance. The 

 relationships between sex hormones, gut microbiome, and host 

 glycaemic and/or lipid metabolism are largely unknown even in 

 the homoeostasis status. Yet this knowledge gap would be pivotal 

 to pinpoint to key mechanisms that are likely to be disrupted in 

 disease context. Methods and results: Here we present the 

 Women4Health (W4H) cohort, a unique cohort comprising up to 300 

 healthy women followed up during a natural menstrual cycle, set 

 up with the primary goal to investigate the combined role of sex 

 hormones and gut microbiota variations in regulating host lipid 

 and glucose metabolism during homoeostasis, using a multi-omics 

 strategy. Additionally, the W4H cohort will take into 

 consideration another ecosystem that is unique to women, the 

 vaginal microbiome, investigating its interaction with gut 

 microbiome and exploring-for the first time-its role in 

 cardiometabolic disorders. Conclusion: The W4H cohort study lays 

 a foundation for improving current knowledge of women-specific 

 mechanisms in cardiometabolic regulation. It aspires to 

 transform insights on host-microbiota interactions into 

 prevention and therapeutic approaches for personalized health 

 care."},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid38280995,

title = {Combination of mutations in genes controlling DNA repair and high mutational load plays a prognostic role in pancreatic ductal adenocarcinoma (PDAC): a retrospective real-life study in Sardinian population},

author = {Maria Cristina Sini and Maria Grazia Doro and Laura Frogheri and Angelo Zinellu and Panagiotis Paliogiannis and Alberto Porcu and Fabrizio Scognamillo and Daniele Delogu and Davide Adriano Santeufemia and Ivana Persico and Grazia Palomba and Giovanni Battista Maestrale and Antonio Cossu and Giuseppe Palmieri},

doi = {10.1186/s12967-024-04923-3},

issn = {1479-5876},

year  = {2024},

date = {2024-01-27},

urldate = {2024-01-27},

journal = {J Transl Med},

volume = {22},

number = {1},

pages = {108},

abstract = {BACKGROUND: Patients with pancreatic ductal adenocarcinoma (PDCA) carrying impaired mismatch repair mechanisms seem to have an outcome advantage under treatment with conventional chemotherapy, whereas the role for the tumor mutation burden on prognosis is controversial. In this study, we evaluated the prognostic role of the mutated genes involved in genome damage repair in a real-life series of PDAC patients in a hospital-based manner from the main Institution deputed to surgically treat such a disease in North Sardinia.



METHODS: A cohort of fifty-five consecutive PDAC patients with potentially resectable/border line resectable PDAC (stage IIB-III) or oligometastatic disease (stage IV) and tumor tissue availability underwent next-generation sequencing (NGS)-based analysis using a panel containing driver oncogenes and tumor suppressor genes as well as genes controlling DNA repair mechanisms.



RESULTS: Genes involved in the both genome damage repair (DR) and DNA mismatch repair (MMR) were found mutated in 17 (31%) and 15 (27%) cases, respectively. One fourth of PDAC cases (14/55; 25.5%) carried tumors presenting a combination of mutations in repair genes (DR and MMR) and the highest mutation load rates (MLR-H). After correction for confounders (surgery, adjuvant therapy, stage T, and metastasis), multivariate Cox regression analysis indicated that mutations in DR genes (HR = 3.0126, 95% CI 1.0707 to 8.4764, p = 0.0367) and the MLR (HR = 1.0018, 95%CI 1.0005 to 1.0032, p = 0.009) were significantly related to worse survival.



CONCLUSIONS: The combination of mutated repair genes and MLR-H, which is associated with a worse survival in our series of PDAC patients treated with conventional chemotherapy protocols, might become a predictive biomarker of response to immunotherapy in addition to its prognostic role in predicting survival.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = {Sequential immunotherapy and targeted therapy for metastatic BRAF V600 mutated melanoma: 4-year survival and biomarkers evaluation from the phase II SECOMBIT trial},

author = {Paolo A. Ascierto and Milena Casula and Jenny Bulgarelli and Marina Pisano and Claudia Piccinini and Luisa Piccin and Antonio Cossu and Mario Mandalà and Pier Francesco Ferrucci and Massimo Guidoboni and Piotr Rutkowski and Virginia Ferraresi and Ana Arance and Michele Guida and Evaristo Maiello and Helen Gogas and Erika Richtig and Maria Teresa Fierro and Celeste Lebbe and Hildur Helgadottir and Paola Queirolo and Francesco Spagnolo and Marco Tucci and Michele Del Vecchio and Maria Gonzales Cao and Alessandro Marco Minisini and Sabino De Placido and Miguel F. Sanmamed and Domenico Mallardo and Miriam Paone and Maria Grazia Vitale and Ignacio Melero and Antonio M. Grimaldi and Diana Giannarelli and Reinhard Dummer and Vanna Chiarion Sileni and Giuseppe Palmieri.},

url = {https://irgb.cnr.it/wp-content/uploads/2024/05/Ascierto-et-al-2024-Nat-Comm.pdf},

doi = {https://doi.org/10.1038/s41467-023-44475-6},

year  = {2024},

date = {2024-01-15},

urldate = {2024-01-15},

journal = {Nature Communications},

volume = {15},

number = {146},

abstract = {No prospective data were available prior to 2021 to inform selection between combination BRAF and MEK inhibition versus dual blockade of programmed cell death protein-1 (PD-1) and cytotoxic T lymphocyte antigen-4 (CTLA-4) as first-line treatment options for BRAFV600-mutant melanoma. SECOMBIT (NCT02631447) was a randomized, three-arm, non comparative phase II trial in which patients were randomized to one of two sequences with immunotherapy or targeted therapy first, with a third arm in which an 8-week induction course of targeted therapy followed by a planned switch to immunotherapy was the first treatment. BRAF/MEK inhibitors were encorafenib plus binimetinib and checkpoint inhibitors ipilimumab plus nivolumab. Primary outcome of overall survival was previously reported, demonstrating improved survival with immunotherapy administered until progression and followed by BRAF/MEK inhibition. Here we report 4-year survival outcomes, confirming long term benefit with first-line immunotherapy. We also describe preliminary results of predefined biomarkers analyses that identify a trend toward improved 4-year overall survival and total progression-free survival in patients

with loss-of-function mutations affecting JAK or low baseline levels of serum interferon gamma (IFNy). These long-term survival outcomes confirm immunotherapy as the preferred first-line treatment approach for most patients with BRAFV600-mutant metastatic melanoma, and the biomarker analyses are hypothesis-generating for future investigations of predictors of durable benefit with dual checkpoint blockade and targeted therapy.

},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Zhernakova2024-gv,

title = {Host genetic regulation of human gut microbial structural 

 variation},

author = {Daria V Zhernakova and Daoming Wang and Lei Liu and Sergio Andreu-Sánchez and Yue Zhang and Angel J Ruiz-Moreno and Haoran Peng and Niels Plomp and Ángela Del Castillo-Izquierdo and Ranko Gacesa and Esteban A Lopera-Maya and Godfrey S Temba and Vesla I Kullaya and Sander S Leeuwen and Lifelines Cohort Study and Ramnik J Xavier and Quirijn Mast and Leo A B Joosten and Niels P Riksen and Joost H W Rutten and Mihai G Netea and Serena Sanna and Cisca Wijmenga and Rinse K Weersma and Alexandra Zhernakova and Hermie J M Harmsen and Jingyuan Fu},

year  = {2024},

date = {2024-01-01},

journal = {Nature},

volume = {625},

number = {7996},

pages = {813--821},

publisher = {Springer Science and Business Media LLC},

abstract = {Älthough the impact of host genetics on gut microbial diversity 

 and the abundance of specific taxa is well established1-6, 

 little is known about how host genetics regulates the genetic 

 diversity of gut microorganisms. Here we conducted a 

 meta-analysis of associations between human genetic variation 

 and gut microbial structural variation in 9,015 individuals from 

 four Dutch cohorts. Strikingly, the presence rate of a 

 structural variation segment in Faecalibacterium prausnitzii 

 that harbours an N-acetylgalactosamine (GalNAc) utilization gene 

 cluster is higher in individuals who secrete the type A 

 oligosaccharide antigen terminating in GalNAc, a feature that is 

 jointly determined by human ABO and FUT2 genotypes, and we could 

 replicate this association in a Tanzanian cohort. In vitro 

 experiments demonstrated that GalNAc can be used as the sole 

 carbohydrate source for F. prausnitzii strains that carry the 

 GalNAc-metabolizing pathway. Further in silico and in vitro 

 studies demonstrated that other ABO-associated species can also 

 utilize GalNAc, particularly Collinsella aerofaciens. The GalNAc 

 utilization genes are also associated with the host's 

 cardiometabolic health, particularly in individuals with mucosal 

 A-antigen. Together, the findings of our study demonstrate that 

 genetic associations across the human genome and bacterial 

 metagenome can provide functional insights into the reciprocal 

 host-microbiome relationship."},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Simbula2023-rj,

title = {miR-365-3p mediates BCL11A and SOX6 erythroid-specific 

 coregulation: A new player in HbF activation},

author = {Michela Simbula and Maria Francesca Manchinu and Maura Mingoia and Mauro Pala and Isadora Asunis and Cristian Antonio Caria and Lucia Perseu and Manan Shah and Merlin Crossley and Paolo Moi and Maria Serafina Ristaldi},

year  = {2023},

date = {2023-12-01},

journal = {Mol. Ther. Nucleic Acids},

volume = {34},

number = {102025},

pages = {102025},

publisher = {Elsevier BV},

abstract = {Hemoglobin switching is a complex biological process not yet 

 fully elucidated. The mechanism regulating the suppression of 

 fetal hemoglobin (HbF) expression is of particular interest 

 because of the positive impact of HbF on the course of diseases 

 such as $beta$-thalassemia and sickle cell disease, hereditary 

 hemoglobin disorders that affect the health of countless 

 individuals worldwide. Several transcription factors have been 

 implicated in the control of HbF, of which BCL11A has emerged as 

 a major player in HbF silencing. SOX6 has also been implicated 

 in silencing HbF and is critical to the silencing of the mouse 

 embryonic hemoglobins. BCL11A and SOX6 are co-expressed and 

 physically interact in the erythroid compartment during 

 differentiation. In this study, we observe that BCL11A knockout 

 leads to post-transcriptional downregulation of SOX6 through 

 activation of microRNA (miR)-365-3p. Downregulating SOX6 by 

 transient ectopic expression of miR-365-3p or gene editing 

 activates embryonic and fetal $beta$-like globin gene 

 expression in erythroid cells. The synchronized expression of 

 BCL11A and SOX6 is crucial for hemoglobin switching. In this 

 study, we identified a BCL11A/miR-365-3p/SOX6 evolutionarily 

 conserved pathway, providing insights into the regulation of the 

 embryonic and fetal globin genes suggesting new targets for 

 treating $beta$-hemoglobinopathies.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37895071,

title = {Inhibitory Effect of Quercetin on Oxidative Endogen Enzymes: A Focus on Putative Binding Modes},

author = {S. Olla and C. Siguri and A. Fais and B. Era and M. C. Fantini and A. "Di Petrillo},

year  = {2023},

date = {2023-10-20},

urldate = {2023-10-20},

journal = {Int J Mol Sci},

volume = {24},

number = {20},

abstract = {Oxidative stress is defined as an imbalance between the production of free radicals and reactive oxygen species (ROS) and the ability of the body to neutralize them by anti-oxidant defense systems. Cells can produce ROS during physiological processes, but excessive ROS can lead to non-specific and irreversible damage to biological molecules, such as DNA, lipids, and proteins. Mitochondria mainly produce endogenous ROS during both physiological and pathological conditions. Enzymes like nicotinamide adenine dinucleotide phosphate oxidase (NOX), xanthine oxidase (XO), lipoxygenase (LOX), myeloperoxidase (MPO), and monoamine oxidase (MAO) contribute to this process. The body has enzymatic and non-enzymatic defense systems to neutralize ROS. The intake of bioactive phenols, like quercetin (Que), can protect against pro-oxidative damage by quenching ROS through a non-enzymatic system. In this study, we evaluate the ability of Que to target endogenous oxidant enzymes involved in ROS production and explore the mechanisms of action underlying its anti-oxidant properties. Que can act as a free radical scavenger by donating electrons through the negative charges in its phenolic and ketone groups. Additionally, it can effectively inhibit the activity of several endogenous oxidative enzymes by binding them with high affinity and specificity. Que had the best molecular docking results with XO, followed by MAO-A, 5-LOX, NOX, and MPO. Que's binding to these enzymes was confirmed by subsequent molecular dynamics, revealing different stability phases depending on the enzyme bound. The 500 ns simulation showed a net evolution of binding for NOX and MPO. These findings suggest that Que has potential as a natural therapy for diseases related to oxidative stress.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37836771,

title = {Synthesis and Characterization of Edaravone Analogues as Remyelinating Agents and Putative Mechanistic Probes},

author = {E. Colombo and S. Olla and C. Minnelli and A. Formato and C. Veroni and S. Corbisiero and M. Pericolo and C. Siguri and G. Mobbili and C. Agresti and P. Seneci},

year  = {2023},

date = {2023-10-04},

volume = {28},

number = {19},

abstract = {as a putative EDA 1 prodrug suitable for in vivo testing.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Gussak2023-rj,

title = {Precision genome engineering in streptococcus suis based on a 

 broad-host-range vector and CRISPR-Cas9 technology},

author = {Alex Gussak and Maria Laura Ferrando and Mels Schrama and Peter Baarlen and Jerry Mark Wells},

year  = {2023},

date = {2023-09-01},

journal = {ÄCS Synth. Biol."},

volume = {12},

number = {9},

pages = {2546--2560},

abstract = {Streptococcussuis is an important zoonotic pathogen that causes 

 severe invasive disease in pigs and humans. Current methods for 

 genome engineering of S. suis rely on the insertion of antibiotic 

 resistance markers, which is time-consuming and labor-intensive 

 and does not allow the precise introduction of small genomic 

 mutations. Here we developed a system for CRISPR-based genome 

 editing in S. suis, utilizing linear DNA fragments for homologous 

 recombination (HR) and a plasmid-based negative selection system 

 for bacteria not edited by HR. To enable the use of this system 

 in other bacteria, we engineered a broad-host-range replicon in 

 the CRISPR plasmid. We demonstrated the utility of this system to 

 rapidly introduce multiple gene deletions in successive rounds of 

 genome editing and to make precise nucleotide changes in 

 essential genes. Furthermore, we characterized a mechanism by 

 which S. suis can escape killing by a targeted Cas9-sgRNA complex 

 in the absence of HR. A characteristic of this new mechanism is 

 the presence of very slow-growing colonies in a persister-like 

 state that may allow for DNA repair or the introduction of 

 mutations, alleviating Cas9 pressure. This does not impact the 

 utility of CRISPR-based genome editing because the escape 

 colonies are easily distinguished from genetically edited clones 

 due to their small colony size. Our CRISPR-based editing system 

 is a valuable addition to the genetic toolbox for engineering of 

 S. suis, as it accelerates the process of mutant construction and 

 simplifies the removal of antibiotic markers between successive 

 rounds of genome editing.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Orru2023-vp,

title = {Biomarker dynamics affecting neoadjuvant therapy response and 

 outcome of HER2-positive breast cancer subtype},

author = {Sandra Örr`u and Emanuele Pascariello and Barbara Pes and Vincenzo Rallo and Raffaele Barbara and Marta Muntoni and Francesca Notari and Gianfranco Fancello and Cristina Mocci and Maria Rosaria Muroni and Paolo Cossu-Rocca and Andrea Angius and Maria Rosaria" De Miglio},

year  = {2023},

date = {2023-08-01},

journal = {Sci. Rep.},

volume = {13},

number = {1},

pages = {12869},

publisher = {Springer Science and Business Media LLC},

abstract = {HER2+ breast cancer (BC) is an aggressive subtype genetically 

 and biologically heterogeneous. We evaluate the predictive and 

 prognostic role of HER2 protein/gene expression levels combined 

 with clinico-pathologic features in 154 HER2+ BCs patients who 

 received trastuzumab-based neoadjuvant chemotherapy (NACT). The 

 tumoral pathological complete response (pCR) rate was 40.9%. 

 High tumoral pCR show a scarce mortality rate vs subjects with a 

 lower response. 93.7% of ypT0 were HER2 IHC3+ BC, 6.3% were 

 HER2 IHC 2+/SISH+ and 86.7% of ypN0 were HER2 IHC3+, the 

 remaining were HER2 IHC2+/SISH+. Better pCR rate correlate with 

 a high percentage of infiltrating immune cells and right-sided 

 tumors, that reduce distant metastasis and improve survival, but 

 no incidence difference. HER2 IHC score and laterality emerge as 

 strong predictors of tumoral pCR after NACT from machine 

 learning analysis. HER2 IHC3+ and G3 are poor prognostic factors 

 for HER2+ BC patients, and could be considered in the 

 application of neoadjuvant therapy. Increasing TILs 

 concentrations, lower lymph node ratio and lower residual tumor 

 cellularity are associated with a better outcome. The immune 

 microenvironment and scarce lymph node involvement have crucial 

 role in clinical outcomes. The combination of all predictors 

 might offer new options for NACT effectiveness prediction and 

 stratification of HER2+ BC during clinical decision-making.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = {BRAFV600 variant allele frequency predicts outcome in metastatic melanoma patients treated with BRAF and MEK inhibitors.},

author = {Mandalà Mario and Palmieri Giuseppe and Ludovini Vienna and Baglivo Sara and Marasciulo Francesca and Castiglione Francesca and Gili Alessio and Osella Abate Simona and Rubatto Marco and Senetta Rebecca and Avallone Gianluca and Ribero Simone and Romano Luca and Pimpinelli Nicola and de Giorgi Vincenzo and Roila Fausto and Pisano Marina and Casula Milena and Manca Antonella and Sini Maria Cristina},

doi = {10.1111/jdv.19281},

year  = {2023},

date = {2023-06-27},

urldate = {2023-06-27},

journal = {Journal of the European Academy of Dermatology & Venereology},

abstract = {Background: The prognostic impact of variant allele frequency (VAF) on clinical outcome in BRAFV600 mutated metastatic melanoma patients (MMPs) receiving BRAF (BRAFi) and MEK inhibitors (MEKi) is unclear. Materials and methods: A cohort of MMPs receiving first line BRAFi and MEKi was identified by inspecting dedicated databases of three Italian Melanoma Intergroup centres. VAF was determined by next generation sequencing in pre-treatment baseline tissue samples. Correlation between VAF and BRAF copy number variation was analysed in an ancillary study by using a training and a validation cohort of melanoma tissue samples and cell lines.Results: Overall, 107 MMPs were included in the study. The VAF cut-off determined by ROC curve was 41.3%. At multivariate analysis, progression-free survival (PFS) was significantly shorter in patients with M1c/M1d [HR 2.25 (95% CI 1.41-3.6, p < 0.01)], in those with VAF >41.3% [HR 1.62 (95% CI 1.04-2.54, p < 0.05)] and in those with ECOG PS ≥1 [HR 1.82 (95% CI 1.15-2.88, p < 0.05)]. Overall survival (OS) was significantly shorter in patients with M1c/M1d [HR 2.01 (95% CI 1.25-3.25, p < 0.01)]. Furthermore, OS was shorter in patients with VAF >41.3% [HR 1.46 (95% CI 0.93-2.29, p = 0.06)] and in patients with ECOG PS ≥1 [HR 1.52 (95% CI 0.94-2.87, p = 0.14)]. BRAF gene amplification was found in 11% and 7% of samples in the training and validation cohort, respectively. Conclusions: High VAF is an independent poor prognostic factor in MMP receiving BRAFi and MEKi. High VAF and BRAF amplification coexist in 7%-11% of patients. },

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Ahuja2023-spd,

title = {Immune resilience despite inflammatory stress promotes longevity 

 and favorable health outcomes including resistance to infection},

author = {Sunil K Ähuja and Muthu Saravanan Manoharan and Grace C Lee and Lyle R McKinnon and Justin A Meunier and Maristella Steri and Nathan Harper and Edoardo Fiorillo and Alisha M Smith and Marcos I Restrepo and Anne P Branum and Matthew J Bottomley and Valeria Orr`u and Fabio Jimenez and Andrew Carrillo and Lavanya Pandranki and Caitlyn A Winter and Lauryn A Winter and Alvaro A Gaitan and Alvaro G Moreira and Elizabeth A Walter and Guido Silvestri and Christopher L King and Yong-Tang Zheng and Hong-Yi Zheng and Joshua Kimani and T Blake Ball and Francis A Plummer and Keith R Fowke and Paul N Harden and Kathryn J Wood and Martin T Ferris and Jennifer M Lund and Mark T Heise and Nigel Garrett and Kristen R Canady and Salim S Abdool Karim and Susan J Little and Sara Gianella and Davey M Smith and Scott Letendre and Douglas D Richman and Francesco Cucca and Hanh Trinh and Sandra Sanchez-Reilly and Joan M Hecht and Jose A Cadena Zuluaga and Antonio Anzueto and Jacqueline A Pugh and South Texas Veterans Health Care System COVID-19 team and Brian K Agan and Robert Root-Bernstein and Robert A Clark and Jason F Okulicz and Weijing" He},

year  = {2023},

date = {2023-06-01},

journal = {Nat. Commun.},

volume = {14},

number = {1},

pages = {3286},

abstract = {Some people remain healthier throughout life than others but the 

 underlying reasons are poorly understood. Here we hypothesize 

 this advantage is attributable in part to optimal immune 

 resilience (IR), defined as the capacity to preserve and/or 

 rapidly restore immune functions that promote disease resistance 

 (immunocompetence) and control inflammation in infectious 

 diseases as well as other causes of inflammatory stress. We gauge 

 IR levels with two distinct peripheral blood metrics that 

 quantify the balance between (i) CD8+ and CD4+ T-cell levels and 

 (ii) gene expression signatures tracking longevity-associated 

 immunocompetence and mortality-associated inflammation. Profiles 

 of IR metrics in ~48,500 individuals collectively indicate that 

 some persons resist degradation of IR both during aging and when 

 challenged with varied inflammatory stressors. With this 

 resistance, preservation of optimal IR tracked (i) a lower risk 

 of HIV acquisition, AIDS development, symptomatic influenza 

 infection, and recurrent skin cancer; (ii) survival during 

 COVID-19 and sepsis; and (iii) longevity. IR degradation is 

 potentially reversible by decreasing inflammatory stress. 

 Overall, we show that optimal IR is a trait observed across the 

 age spectrum, more common in females, and aligned with a specific 

 immunocompetence-inflammation balance linked to favorable 

 immunity-dependent health outcomes. IR metrics and mechanisms 

 have utility both as biomarkers for measuring immune health and 

 for improving health outcomes.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Ahuja2023-spc,

title = {Immune resilience despite inflammatory stress promotes longevity 

 and favorable health outcomes including resistance to infection},

author = {Sunil K Ähuja and Muthu Saravanan Manoharan and Grace C Lee and Lyle R McKinnon and Justin A Meunier and Maristella Steri and Nathan Harper and Edoardo Fiorillo and Alisha M Smith and Marcos I Restrepo and Anne P Branum and Matthew J Bottomley and Valeria Orr`u and Fabio Jimenez and Andrew Carrillo and Lavanya Pandranki and Caitlyn A Winter and Lauryn A Winter and Alvaro A Gaitan and Alvaro G Moreira and Elizabeth A Walter and Guido Silvestri and Christopher L King and Yong-Tang Zheng and Hong-Yi Zheng and Joshua Kimani and T Blake Ball and Francis A Plummer and Keith R Fowke and Paul N Harden and Kathryn J Wood and Martin T Ferris and Jennifer M Lund and Mark T Heise and Nigel Garrett and Kristen R Canady and Salim S Abdool Karim and Susan J Little and Sara Gianella and Davey M Smith and Scott Letendre and Douglas D Richman and Francesco Cucca and Hanh Trinh and Sandra Sanchez-Reilly and Joan M Hecht and Jose A Cadena Zuluaga and Antonio Anzueto and Jacqueline A Pugh and South Texas Veterans Health Care System COVID-19 team and Brian K Agan and Robert Root-Bernstein and Robert A Clark and Jason F Okulicz and Weijing" He},

year  = {2023},

date = {2023-06-01},

journal = {Nat. Commun.},

volume = {14},

number = {1},

pages = {3286},

abstract = {Some people remain healthier throughout life than others but the 

 underlying reasons are poorly understood. Here we hypothesize 

 this advantage is attributable in part to optimal immune 

 resilience (IR), defined as the capacity to preserve and/or 

 rapidly restore immune functions that promote disease resistance 

 (immunocompetence) and control inflammation in infectious 

 diseases as well as other causes of inflammatory stress. We gauge 

 IR levels with two distinct peripheral blood metrics that 

 quantify the balance between (i) CD8+ and CD4+ T-cell levels and 

 (ii) gene expression signatures tracking longevity-associated 

 immunocompetence and mortality-associated inflammation. Profiles 

 of IR metrics in ~48,500 individuals collectively indicate that 

 some persons resist degradation of IR both during aging and when 

 challenged with varied inflammatory stressors. With this 

 resistance, preservation of optimal IR tracked (i) a lower risk 

 of HIV acquisition, AIDS development, symptomatic influenza 

 infection, and recurrent skin cancer; (ii) survival during 

 COVID-19 and sepsis; and (iii) longevity. IR degradation is 

 potentially reversible by decreasing inflammatory stress. 

 Overall, we show that optimal IR is a trait observed across the 

 age spectrum, more common in females, and aligned with a specific 

 immunocompetence-inflammation balance linked to favorable 

 immunity-dependent health outcomes. IR metrics and mechanisms 

 have utility both as biomarkers for measuring immune health and 

 for improving health outcomes.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Ahuja2023-spb,

title = {Immune resilience despite inflammatory stress promotes longevity 

 and favorable health outcomes including resistance to infection},

author = {Sunil K Ähuja and Muthu Saravanan Manoharan and Grace C Lee and Lyle R McKinnon and Justin A Meunier and Maristella Steri and Nathan Harper and Edoardo Fiorillo and Alisha M Smith and Marcos I Restrepo and Anne P Branum and Matthew J Bottomley and Valeria Orr`u and Fabio Jimenez and Andrew Carrillo and Lavanya Pandranki and Caitlyn A Winter and Lauryn A Winter and Alvaro A Gaitan and Alvaro G Moreira and Elizabeth A Walter and Guido Silvestri and Christopher L King and Yong-Tang Zheng and Hong-Yi Zheng and Joshua Kimani and T Blake Ball and Francis A Plummer and Keith R Fowke and Paul N Harden and Kathryn J Wood and Martin T Ferris and Jennifer M Lund and Mark T Heise and Nigel Garrett and Kristen R Canady and Salim S Abdool Karim and Susan J Little and Sara Gianella and Davey M Smith and Scott Letendre and Douglas D Richman and Francesco Cucca and Hanh Trinh and Sandra Sanchez-Reilly and Joan M Hecht and Jose A Cadena Zuluaga and Antonio Anzueto and Jacqueline A Pugh and South Texas Veterans Health Care System COVID-19 team and Brian K Agan and Robert Root-Bernstein and Robert A Clark and Jason F Okulicz and Weijing" He},

year  = {2023},

date = {2023-06-01},

journal = {Nat. Commun.},

volume = {14},

number = {1},

pages = {3286},

abstract = {Some people remain healthier throughout life than others but the 

 underlying reasons are poorly understood. Here we hypothesize 

 this advantage is attributable in part to optimal immune 

 resilience (IR), defined as the capacity to preserve and/or 

 rapidly restore immune functions that promote disease resistance 

 (immunocompetence) and control inflammation in infectious 

 diseases as well as other causes of inflammatory stress. We gauge 

 IR levels with two distinct peripheral blood metrics that 

 quantify the balance between (i) CD8+ and CD4+ T-cell levels and 

 (ii) gene expression signatures tracking longevity-associated 

 immunocompetence and mortality-associated inflammation. Profiles 

 of IR metrics in ~48,500 individuals collectively indicate that 

 some persons resist degradation of IR both during aging and when 

 challenged with varied inflammatory stressors. With this 

 resistance, preservation of optimal IR tracked (i) a lower risk 

 of HIV acquisition, AIDS development, symptomatic influenza 

 infection, and recurrent skin cancer; (ii) survival during 

 COVID-19 and sepsis; and (iii) longevity. IR degradation is 

 potentially reversible by decreasing inflammatory stress. 

 Overall, we show that optimal IR is a trait observed across the 

 age spectrum, more common in females, and aligned with a specific 

 immunocompetence-inflammation balance linked to favorable 

 immunity-dependent health outcomes. IR metrics and mechanisms 

 have utility both as biomarkers for measuring immune health and 

 for improving health outcomes.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Ahuja2023-sp,

title = {Immune resilience despite inflammatory stress promotes longevity  and favorable health outcomes including resistance to infection},

author = {Sunil K Ähuja and Muthu Saravanan Manoharan and Grace C Lee and Lyle R McKinnon and Justin A Meunier and Maristella Steri and Nathan Harper and Edoardo Fiorillo and Alisha M Smith and Marcos I Restrepo and Anne P Branum and Matthew J Bottomley and Valeria Orr`u and Fabio Jimenez and Andrew Carrillo and Lavanya Pandranki and Caitlyn A Winter and Lauryn A Winter and Alvaro A Gaitan and Alvaro G Moreira and Elizabeth A Walter and Guido Silvestri and Christopher L King and Yong-Tang Zheng and Hong-Yi Zheng and Joshua Kimani and T Blake Ball and Francis A Plummer and Keith R Fowke and Paul N Harden and Kathryn J Wood and Martin T Ferris and Jennifer M Lund and Mark T Heise and Nigel Garrett and Kristen R Canady and Salim S Abdool Karim and Susan J Little and Sara Gianella and Davey M Smith and Scott Letendre and Douglas D Richman and Francesco Cucca and Hanh Trinh and Sandra Sanchez-Reilly and Joan M Hecht and Jose A Cadena Zuluaga and Antonio Anzueto and Jacqueline A Pugh and South Texas Veterans Health Care System COVID-19 team and Brian K Agan and Robert Root-Bernstein and Robert A Clark and Jason F Okulicz and Weijing" He},

doi = {10.1038/s41467-023-38238-6},

year  = {2023},

date = {2023-06-01},

urldate = {2023-06-01},

journal = {Nat. Commun.},

volume = {14},

number = {1},

pages = {3286},

abstract = {Some people remain healthier throughout life than others but the 

 underlying reasons are poorly understood. Here we hypothesize 

 this advantage is attributable in part to optimal immune 

 resilience (IR), defined as the capacity to preserve and/or 

 rapidly restore immune functions that promote disease resistance 

 (immunocompetence) and control inflammation in infectious 

 diseases as well as other causes of inflammatory stress. We gauge 

 IR levels with two distinct peripheral blood metrics that 

 quantify the balance between (i) CD8+ and CD4+ T-cell levels and 

 (ii) gene expression signatures tracking longevity-associated 

 immunocompetence and mortality-associated inflammation. Profiles 

 of IR metrics in ~48,500 individuals collectively indicate that 

 some persons resist degradation of IR both during aging and when 

 challenged with varied inflammatory stressors. With this 

 resistance, preservation of optimal IR tracked (i) a lower risk 

 of HIV acquisition, AIDS development, symptomatic influenza 

 infection, and recurrent skin cancer; (ii) survival during 

 COVID-19 and sepsis; and (iii) longevity. IR degradation is 

 potentially reversible by decreasing inflammatory stress. 

 Overall, we show that optimal IR is a trait observed across the 

 age spectrum, more common in females, and aligned with a specific 

 immunocompetence-inflammation balance linked to favorable 

 immunity-dependent health outcomes. IR metrics and mechanisms 

 have utility both as biomarkers for measuring immune health and 

 for improving health outcomes.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Ahuja2023-yn,

title = {Immune resilience despite inflammatory stress promotes longevity 

 and favorable health outcomes including resistance to infection},

author = {Sunil K Ähuja and Muthu Saravanan Manoharan and Grace C Lee and Lyle R McKinnon and Justin A Meunier and Maristella Steri and Nathan Harper and Edoardo Fiorillo and Alisha M Smith and Marcos I Restrepo and Anne P Branum and Matthew J Bottomley and Valeria Orr`u and Fabio Jimenez and Andrew Carrillo and Lavanya Pandranki and Caitlyn A Winter and Lauryn A Winter and Alvaro A Gaitan and Alvaro G Moreira and Elizabeth A Walter and Guido Silvestri and Christopher L King and Yong-Tang Zheng and Hong-Yi Zheng and Joshua Kimani and T Blake Ball and Francis A Plummer and Keith R Fowke and Paul N Harden and Kathryn J Wood and Martin T Ferris and Jennifer M Lund and Mark T Heise and Nigel Garrett and Kristen R Canady and Salim S Abdool Karim and Susan J Little and Sara Gianella and Davey M Smith and Scott Letendre and Douglas D Richman and Francesco Cucca and Hanh Trinh and Sandra Sanchez-Reilly and Joan M Hecht and Jose A Cadena Zuluaga and Antonio Anzueto and Jacqueline A Pugh and South Texas Veterans Health Care System COVID-19 team and Brian K Agan and Robert Root-Bernstein and Robert A Clark and Jason F Okulicz and Weijing" He},

year  = {2023},

date = {2023-06-01},

journal = {Nat. Commun.},

volume = {14},

number = {1},

pages = {3286},

abstract = {Some people remain healthier throughout life than others but the 

 underlying reasons are poorly understood. Here we hypothesize 

 this advantage is attributable in part to optimal immune 

 resilience (IR), defined as the capacity to preserve and/or 

 rapidly restore immune functions that promote disease resistance 

 (immunocompetence) and control inflammation in infectious 

 diseases as well as other causes of inflammatory stress. We gauge 

 IR levels with two distinct peripheral blood metrics that 

 quantify the balance between (i) CD8+ and CD4+ T-cell levels and 

 (ii) gene expression signatures tracking longevity-associated 

 immunocompetence and mortality-associated inflammation. Profiles 

 of IR metrics in ~48,500 individuals collectively indicate that 

 some persons resist degradation of IR both during aging and when 

 challenged with varied inflammatory stressors. With this 

 resistance, preservation of optimal IR tracked (i) a lower risk 

 of HIV acquisition, AIDS development, symptomatic influenza 

 infection, and recurrent skin cancer; (ii) survival during 

 COVID-19 and sepsis; and (iii) longevity. IR degradation is 

 potentially reversible by decreasing inflammatory stress. 

 Overall, we show that optimal IR is a trait observed across the 

 age spectrum, more common in females, and aligned with a specific 

 immunocompetence-inflammation balance linked to favorable 

 immunity-dependent health outcomes. IR metrics and mechanisms 

 have utility both as biomarkers for measuring immune health and 

 for improving health outcomes.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37232846,

title = {PD-L1 Expression in Cutaneous Angiosarcomas: A Systematic Review with Meta-Analysis},

author = {Renato Lobrano and Panagiotis Paliogiannis and Angelo Zinellu and Giuseppe Palmieri and Ivana Persico and Arduino A Mangoni and Antonio Cossu},

doi = {10.3390/curroncol30050388},

issn = {1718-7729},

year  = {2023},

date = {2023-05-17},

urldate = {2023-05-17},

journal = {Curr Oncol},

volume = {30},

number = {5},

pages = {5135--5144},

abstract = {Cutaneous angiosarcoma (CAS) is the most common type of angiosarcoma that predominantly affects older Caucasians. The outcomes of immunotherapy in CAS are currently under investigation in relation to the expression of programmed death ligand 1 (PD-L1) and other biomarkers. We performed a systematic review and metanalysis of data from the current literature reporting on PD-L1 immunohistochemistry expression. A systematic search of publications in the electronic databases PubMed, Web of Science, and Scopus was conducted using the following terms: "PD-L1" and "angiosarcomas". A total of ten studies reporting on 279 cases were identified and included in the meta-analysis. The pooled prevalence of PD-L1 expression in CAS was 54% (95% CI 36-71%), with high heterogeneity (I = 84.81%,  < 0.001). In sub-group analysis, the proportion of PD-L1 expression in CAS was significantly ( = 0.049) lower in Asian studies (ES = 35%, 95% CI 28-42%, I = 0.0%,  = 0.46) than in European studies (ES = 71%, 95% CI 51-89%, I = 48.91%,  = 0.12).},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = {Comparison between Three Different Techniques for the Detection of EGFR Mutations in Liquid Biopsies of Patients with Advanced Stage Lung Adenocarcinoma},

author = {Casula Milena and Pisano Marina and Paliogiannis Panagiotis and Colombino Maria and Sini Maria Cristina and Zinellu Angelo},

year  = {2023},

date = {2023-03-29},

urldate = {2023-03-29},

journal = {International Journal of Molecular Sciences},

volume = {24},

number = {6410},

abstract = {Oncogenic mutations in the EGFR gene are targets of tyrosine kinase inhibitors (TKIs) in lung adenocarcinoma (LC) patients and their search is mandatory to make decisions on treatment strategies. Liquid biopsy of circulating tumour DNA (ctDNA) is increasingly used to detect EGFR mutations including main activating alterations (exon 19 deletions and exon 21 L858R mutation) and T790M mutation which is the most common mechanism of acquired resistance to first- and second-generation TKIs. In this study we prospectively compared three different techniques for EGFR mutation detection in liquid biopsies of such patients. Fifty-four ctDNA samples from 48 consecutive advanced LC patients treated with TKIs were tested for relevant EGFR mutations with Therascreen® EGFR Plasma RGQ-PCR Kit (Qiagen). Samples were subsequently tested with two different technologies with the aim to compare the EGFR detection rates: real-time PCR based Idylla™ ctEGFR mutation assay (Biocartis) and next-generation sequencing (NGS) system with Ion AmpliSeq Cancer Hotspot panel (ThermoFisher). A high concordance rate for main druggable EGFR alterations was observed with the two real-time PCR-based assays ranging from 100% for T790M mutation to 94% for L858R variant and 85% for exon 19 deletions. Conversely lower concordance rates were found between real-time PCR approaches and the NGS method (L858R: 88%; exon19-dels: 74%; T790M: 37.5%). Our results evidenced an equivalent detection ability between PCR-based techniques for circulating EGFR mutations. The NGS assay allowed detection of a wider range of EGFR mutations but showed a poor ability to detect T790M.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Serra2023-ve,

title = {Polygenic risk score and biochemical/environmental variables 

 predict a low-risk profile of age-related macular degeneration 

 in Sardinia},

author = {Rita Serra and Vincenzo Rallo and Antonio Pinna and Maristella Steri and Maria Grazia Piras and Michele Marongiu and Florence Coscas and Myriam Gorospe and David Schlessinger and Edoardo Fiorillo and Francesco Cucca and Andrea Angius},

year  = {2023},

date = {2023-03-01},

journal = {Ärbeitsphysiologie"},

volume = {261},

number = {3},

pages = {691--698},

publisher = {Springer Science and Business Media LLC},

abstract = {PURPOSE: To ascertain the prevalence and clinical and genetic 

 features of age-related macular degeneration (AMD) in subjects 

 living in the Lanusei valley, Central Sardinia, Italy, involved 

 in a study on ageing (SardiNIA project). METHODS: A total of 814 

 volunteers aged $geq$ 50 years, randomly selected from the 

 SardiNIA project dataset, were included. A color fundus (CF) 

 photograph of the 30° central retina of each eye was obtained 

 and graded according to the Age-Related Eye Disease Study 

 system. Life-style choices were investigated using standardized 

 questionnaires. The concentrations of several inflammatory 

 biomarkers (i.e., complement component, fibrinogen, and 

 C-reactive protein) were measured. Polygenic risk score (PRS) 

 was calculated and compared with results obtained from a 

 European cohort. RESULTS: A total of 756 subjects had gradable 

 CF photographs for AMD detection. In 91.3%, no signs of AMD 

 were observed. The prevalence rates of early and late AMDs were 

 6.9% and 0.6%, respectively. A total of 85% of subjects were 

 physically active; only 13.5% were current smokers. Low 

 concentrations of complement component, fibrinogen, and 

 C-reactive protein were found. We calculated the polygenic risk 

 scores (PRS) using 40 AMD markers distributed on several 

 candidate genes in Europeans and Sardinians. The mean PRS value 

 was significantly lower in Sardinians than in the Europeans (0.21 vs. 0.248, respectivel},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid36425957,

title = {CFDP1 is a neuroblastoma susceptibility gene that regulates transcription factors of the noradrenergic cell identity},

author = {D. Formicola and V. A. Lasorsa and S. Cantalupo and A. Testori and A. Cardinale and M. Avitabile and S. Diskin and A. Iolascon and M. Capasso},

year  = {2023},

date = {2023-01-01},

urldate = {2023-01-01},

journal = {HGG Adv},

volume = {4},

number = {1},

pages = {100158},

abstract = {acts as oncogene in NB. In addition, we provide evidence that genetic predisposition to NB can be mediated by the alteration of noradrenergic lineage-specific gene expression.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Serra2022-xa,

title = {Quantifying the detrimental effects of multiple freeze/thaw  cycles on primary human lymphocyte survival and function},

author = {Valentina Serra and Edoardo Fiorillo and Francesco Cucca and Valeria Orr`u},

doi = {10.3390/ijms24010634.},

year  = {2022},

date = {2022-12-01},

urldate = {2022-12-01},

journal = {Int. J. Mol. Sci.},

volume = {24},

number = {1},

pages = {634},

publisher = {MDPI AG},

abstract = {The use of cryopreserved peripheral blood mononuclear cells is 

 common in biological research. It is widely accepted that 

 primary cells are rendered unusable by several freezing cycles, 

 although this practice might be very helpful when the biological 

 material is valuable and its re-collection is impractical. To 

 determine the extent to which primary cells undergoing repeated 

 freezing cycles are comparable to one another and to fresh 

 samples, we evaluated overall lymphocyte viability, their 

 proliferation and cytokine production capabilities, as well as 

 the levels of 27 cell subtypes in ten human peripheral blood 

 mononuclear cells frozen for five years and repeatedly thawed. 

 As expected, we observed a progressive increase in cell death 

 percentages on three rounds of thawing, but the frequency of the 

 main lymphocyte subsets was stable across the three thawings. 

 Nevertheless, we observed a significant reduction of B cell 

 frequency in frozen samples compared to fresh ones. On repeated 

 thawings and subsequent conventional stimulation, lymphocyte 

 proliferation significantly decreased, and IL-10, IL-6, GM-CSF, 

 IFN-gamma, and IL-8 showed a trend to lower values.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = {Inhibitory Effect of Curcumin-Inspired Derivatives on Tyrosinase Activity and Melanogenesis},

author = {Gaia Rocchitta and Carla Rozzo and Marina Pisano and Davide Fabbri and Maria Antonietta Dettori and

Paolo Ruzza and Claudia Honisch and Roberto Dallocchio and Alessandro Dessì and Rossana Migheli and

PierAndrea Serra and Giovanna Delogu},

url = {https://doi.org/10.3390/molecules27227942

https://irgb.cnr.it/wp-content/uploads/2024/05/Rocchitta-et-al-2022-2.pdf},

doi = {https://doi.org/10.3390/molecules27227942},

year  = {2022},

date = {2022-11-16},

urldate = {2022-11-16},

journal = {Molecules},

volume = {27},

number = {7942},

pages = {1-24},

abstract = {Tyrosinase is a well-known copper-containing metalloenzyme typically involved in the synthesis of melanin. Recently, curcumin and several synthetic derivatives have been recognized as tyrosinase inhibitors with interesting anti-melanogenic therapeutic activity. In this study, three curcumin-inspired compounds 1, 6 and 7 were prepared in yields ranging from 60 to 88 % and spectrophotometric, electrochemical, in vitro and in silico analyses were carried out. The viability of PC12 cells, a rat pheochromocytoma derived-cell line, with compounds 1, 6 and 7, showed values around 80% at 5 uM concentration. In cell proliferation assays, compounds 1, 6 and 7 did not show significant toxicity on fibroblasts nor melanoma cells up to 10 uM with viability values over 90%. The inhibition of tyrosinase activity was evaluated both by a UV-Vis spectroscopic method at two different concentrations, 0.2 and 2.0 uM, and by amperometric assay with IC50 for compounds 1, 6 and 7 ranging from 11 to 24 nM. Melanin content assays on human melanoma cells were performed to test the capability of compounds to inhibit melanin biosynthesis. All compounds exerted a decrease in melanin content, with compound 7 being the most effective by showing a melanogenesis inhibition up to four times greater than arbutin at 100 uM. Moreover, the antioxidant activity of the selected inhibitors was evaluated against H2O2 in amperometric experiments, whereby compound 7 was about three times more effective compared to compounds 1 and 6. The tyrosinase X-ray structure of Bacterium megaterium crystal was used to carry out molecular docking studies in the presence of compounds 1, 6 and 7 in comparison with that of kojic acid and arbutin, two conventional tyrosinase inhibitors. Molecular docking of compounds 6 and 7 confirmed the high affinity of these compounds to tyrosinase protein.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Chen2022-am,

title = {Influence of the microbiome, diet and genetics on 

 inter-individual variation in the human plasma metabolome},

author = {Lianmin Chen and Daria V Zhernakova and Alexander Kurilshikov and Sergio Andreu-Sánchez and Daoming Wang and Hannah E Augustijn and Arnau Vich Vila and Lifelines Cohort Study and Rinse K Weersma and Marnix H Medema and Mihai G Netea and Folkert Kuipers and Cisca Wijmenga and Alexandra Zhernakova and Jingyuan Fu},

year  = {2022},

date = {2022-11-01},

journal = {Nat. Med.},

volume = {28},

number = {11},

pages = {2333--2343},

publisher = {Springer Science and Business Media LLC},

abstract = {The levels of the thousands of metabolites in the human plasma 

 metabolome are strongly influenced by an individual's genetics 

 and the composition of their diet and gut microbiome. Here, by 

 assessing 1,183 plasma metabolites in 1,368 extensively 

 phenotyped individuals from the Lifelines DEEP and Genome of the 

 Netherlands cohorts, we quantified the proportion of 

 inter-individual variation in the plasma metabolome explained by 

 different factors, characterizing 610, 85 and 38 metabolites as 

 dominantly associated with diet, the gut microbiome and 

 genetics, respectively. Moreover, a diet quality score derived 

 from metabolite levels was significantly associated with diet 

 quality, as assessed by a detailed food frequency questionnaire. 

 Through Mendelian randomization and mediation analyses, we 

 revealed putative causal relationships between diet, the gut 

 microbiome and metabolites. For example, Mendelian randomization 

 analyses support a potential causal effect of Eubacterium 

 rectale in decreasing plasma levels of hydrogen sulfite-a toxin 

 that affects cardiovascular function. Lastly, based on analysis 

 of the plasma metabolome of 311 individuals at two time points 

 separated by 4 years, we observed a positive correlation between 

 the stability of metabolite levels and the amount of variance in 

 the levels of that metabolite that could be explained in our 

 analysis. Altogether, characterization of factors that explain 

 inter-individual variation in the plasma metabolome can help 

 design approaches for modulating diet or the gut microbiome to 

 shape a healthy metabolome.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid36543896,

title = {Analysis of the oral microbiome during hormonal cycle and its alterations in menopausal women: the },

author = {A Tramice and D Paris and A Manca and F A Guevara Agudelo and S Petrosino and L Siracusa and M Carbone and D Melck and F Raymond and F Piscitelli},

doi = {10.1038/s41598-022-26528-w},

issn = {2045-2322},

year  = {2022},

date = {2022-09-21},

journal = {Sci Rep},

volume = {12},

number = {1},

pages = {22086},

abstract = {The maintenance of human health is dependent on a symbiotic relationship between humans and associated bacteria. The diversity and abundance of each habitat's signature microbes vary widely among body areas and among them the oral microbiome plays a key role. Significant changes in the oral cavity, predominantly at salivary and periodontal level, have been associated with changes in estrogen levels. However, whether the oral microbiome is affected by hormonal level alterations is understudied. Hence the main objective pursued by AMICA project was to characterize the oral microbiome (saliva) in healthy women through: profiling studies using "omics" technologies (NMR-based metabolomics, targeted lipidomics by LC-MS, metagenomics by NGS); SinglePlex ELISA assays; glycosidase activity analyses and bioinformatic analysis. For this purpose, thirty-nine medically healthy women aged 26-77 years (19 with menstrual cycle and 20 in menopause) were recruited. Participants completed questionnaires assessing detailed medical and medication history and demographic characteristics. Plasmatic and salivary levels of sexual hormones were assessed (FSH, estradiol, LH and progesteron) at day 3 and 14 for women with menstrual cycle and only once for women in menopause. Salivary microbiome composition was assessed through meta-taxonomic 16S sequencing and overall, the salivary microbiome of most women remained relatively stable throughout the menstrual cycle and in menopause. Targeted lipidomics and untargeted metabolomics profiling were assessed through the use of LC-MS and NMR spectroscopy technologies, respectively and significant changes in terms of metabolites were identified in saliva of post-menopausal women in comparison to cycle. Moreover, glycosyl hydrolase activities were screened and showed that the β-D-hexosaminidase activity was the most present among those analyzed. Although this study has not identified significant alterations in the composition of the oral microbiome, multiomics analysis have revealed a strong correlation between 2-AG and α-mannosidase. In conclusion, the use of a multidisciplinary approach to investigate the oral microbiome of healthy women provided some indication about microbiome-derived predictive biomarkers that could be used in the future for developing new strategies to help to re-establish the correct hormonal balance in post-menopausal women.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid35601448,

title = {Aquivion perfluorosulfonic superacid as an effective catalyst for selective epoxidation of vegetable oils},

author = {Riccardo Polese and Elisa Pintus and Luca Nuvoli and Monica Tiana and Salvatore Pintus and Giuseppe Satta and Andrea Beccu and Silvia Gaspa and Massimo Carraro and Lidia De Luca and Ugo Azzena and Luisa Pisano},

doi = {10.1098/rsos.211554},

issn = {2054-5703},

year  = {2022},

date = {2022-09-06},

journal = {R Soc Open Sci},

volume = {9},

number = {4},

pages = {211554},

abstract = {The acid-promoted epoxidation of vegetable oils was studied using a variety of acidic ion exchange resins as heterogeneous acid catalysts. Quantitative and selective epoxidation of a series of vegetable oils with different composition of saturated, mono-, di- and tri-unsaturated fatty acids was obtained upon identification of the more efficient catalyst and experimental conditions. Furthermore, optimized reaction conditions were successfully applied to the epoxidation of a waste cooking oil, thus extending our procedure to the valorization of a biowaste, an area of increasing importance within a more sustainable society. The use of quantitative HNMR besides making accurate evaluation of the amounts of reagents to be employed and of the selectivity, allowed facile and rapid quantification of mono-, di- and tri-epoxides, thus providing an indirect indication on the fatty acid composition of the vegetable oils, even in the presence of very low quantities of linolenic acid.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}