Danila Vittori

Bio: Danila Vittori is an academic researcher from Sapienza University of Rome. The author has contributed to research in topics: Virus & Gene. The author has an hindex of 4, co-authored 5 publications receiving 593 citations.

A “candidate-interactome” aggregate analysis of genome-wide association data in multiple sclerosis

Abstract: Though difficult, the study of gene-environment interactions in multifactorial diseases is crucial for interpreting the relevance of non-heritable factors and prevents from overlooking genetic associations with small but measurable effects. We propose a "candidate interactome" (i.e. a group of genes whose products are known to physically interact with environmental factors that may be relevant for disease pathogenesis) analysis of genome-wide association data in multiple sclerosis. We looked for statistical enrichment of associations among interactomes that, at the current state of knowledge, may be representative of gene-environment interactions of potential, uncertain or unlikely relevance for multiple sclerosis pathogenesis: Epstein-Barr virus, human immunodeficiency virus, hepatitis B virus, hepatitis C virus, cytomegalovirus, HHV8-Kaposi sarcoma, H1N1-influenza, JC virus, human innate immunity interactome for type I interferon, autoimmune regulator, vitamin D receptor, aryl hydrocarbon receptor and a panel of proteins targeted by 70 innate immune-modulating viral open reading frames from 30 viral species. Interactomes were either obtained from the literature or were manually curated. The P values of all single nucleotide polymorphism mapping to a given interactome were obtained from the last genome-wide association study of the International Multiple Sclerosis Genetics Consortium & the Wellcome Trust Case Control Consortium, 2. The interaction between genotype and Epstein Barr virus emerges as relevant for multiple sclerosis etiology. However, in line with recent data on the coexistence of common and unique strategies used by viruses to perturb the human molecular system, also other viruses have a similar potential, though probably less relevant in epidemiological terms.

Epstein–Barr virus nuclear antigen-1 B-cell epitopes in multiple sclerosis twins

Abstract: Background: Compared with quantitative observations, the search for qualitative changes that may characterize the immune response to Epstein–Barr virus (EBV) in multiple sclerosis (MS) has been less intense.Objective: To examine the B-cell epitopes of antibodies against the Epstein–Barr nuclear antigen-1 (EBNA-1) and their relevance for MS, through a study in disease-discordant identical twins.Methods: We evaluated the antibodies to all unique, maximally overlapping octapeptides of EBNA-1 in 12 pairs of monozygotic (MZ) twins (9 MS-discordant, 3 healthy), 3 non-twin patients and 2 healthy subjects. All except one of the patients were untreated. The EBV serology of these individuals had been assessed in advance using commercially available and in-house enzyme-linked immunosorbent assay (ELISA) kits, including assays for antibodies against select peptides of EBNA-1: EBNA-72 (GAGGGAGAGG) and EBNA-206 (EADYFEYHQEGGPDGE).Results: The glycine–alanine rich domain of EBNA-1 was immunodominant in all subjects. Com...

Serum elements and oxidative status in clinically isolated syndromes: imbalance and predictivity.

Abstract: Background: Metals are suspected of being involved in the pathogenesis of various neurologic diseases. We previously found a complex imbalance in serum chemical elements and oxidative status in patients with clinically definite multiple sclerosis (CDMS). Objective: To understand whether this imbalance affects people with clinically isolated syndrome (CIS) and, if so, whether it predicts conversion to CDMS. Methods: We studied 22 chemical elements and the oxidative status in 49 patients with CIS, 49 patients with CDMS, and 49 healthy donors (HD). Univariate and multivariate approaches were used to identify profiles for each group. A logistic regression analysis was used to identify the predictive potential of baseline data (elements, oxidative status, and MRI findings) for conversion to CDMS over 36 months. Results: Several elements and oxidative status values differed significantly among the 3 groups. Discriminant analysis revealed a major contribution of Ca, Fe, Sn, Zn, serum antioxidant capacity, and serum oxidative status, which resulted in distinct profiles (the prediction of group membership was 96% [cross-validated 92%] for HD, 92% [cross-validated 92%] for CDMS, and 90% [cross-validated 86%] for CIS). A weighted combination of element concentrations and oxidative status values, adjusting for all other predictors, would predict a reduction in the risk of conversion to CDMS within 3 years (odds ratio 0.37; 95% confidence interval 0.18–0.76; p = 0.007), thereby proving more effective than MRI at baseline. Conclusions: The peculiar imbalance in serum elements and oxidative status that characterizes patients with CIS and may predict conversion to CDMS warrants studies on larger sample sizes.

Multiple sclerosis etiology: beyond genes and environment.

Abstract: Multiple sclerosis (MS) is a disorder of the CNS with inflammatory and neurodegenerative components. The etiology is unknown, but there is evidence for a role of both genetic and environmental factors. Among the heritable factors, MHC class II genes are strongly involved, as well as genes coding for others molecules of immunological relevance, genes controlling neurobiological pathways and genes of unknown function. Among nonheritable factors, many infectious agents (mainly viruses) and environmental factors (e.g., smoke, sun exposition and diet) seem to be of etiologic importance. Here, we report and discuss recent findings in MS on largely unexplored fields: the alternative splicing of mRNAs and regulatory noncoding RNAs, the major sources of transcriptome diversity; and epigenetic changes with special attention paid to DNA methylation and histone acetylation, the main regulators of gene expression.

Screening for neurotropic viruses in cerebrospinal fluid of patients with multiple sclerosis and other neurological diseases

Abstract: The paper by Virtanen et al.1 strengthens the association of herpes viruses with multiple sclerosis (MS). The correlation between the presence of Epstein Barr virus (EBV)/Herpes Virus 6 (HHV-6) DNA in cerebrospinal fluid (CSF) and number of contrast enhancing lesions (CELs) on magnetic resonance imaging (MRI) is of interest and mirrors our results from a screening for neurotropic viruses in cerebrospinal fluid of patients with MS and other neurological diseases. We performed PCR for herpes simplex virus 1 (HSV1), herpes simplex virus 2 (HSV2), cytomegalovirus (CMV), varicella zoster virus (VZV), HHV6, JC virus (JCV) and EBV on CSF samples from 159 patients who had had a lumbar puncture for diagnostic purposes. All CSF samples were analyzed using a commercial RHA CNS kit (Labo Bio-medical Products) for the detection of cell-free and cell-associated viral nucleic acids. Patients were then grouped according to their final diagnosis: 60 with MS (58 relapsing–remitting [RR] and two primary progressive [PP]; mean age 37±13 years, 40 females, 20 males), 48 with other inflammatory diseases (OIND; mean age 57±17 years, 23 females, 25 males), and 51 with other non-inflammatory diseases (NIND; mean age 56±18 years, 43 females, 8 males). Gadolinium-enhanced MRI was performed in all patients within 10 days of CSF sampling. In the MS group, 14 patients had a positive PCR for EBV, two for HSV1, three for HSV2 and one for HHV6. In OIND patients, 12 had positive PCR for EBV, two for HSV1, three for HSV2, four for CMV, one for JCV and four for HHV6. In NIND patients, two had positive PCR for EBV, one for HHV6 and one for VZV. The frequency of viral DNA in CSF was comparable among MS and OIND groups. A significant bias in the distribution of EBV was observed in MS and OIND groups with respect to NIND (p = 0.011 at Fisher’s exact test), while CMV infection was more frequent in OIND patients (p = 0.036 at Fisher’s exact test). In patients with MS we observed an excess of large T2 lesions at MRI in cases with EBV DNA in CSF: T2 lesions larger than 10 mm were present in six out 14 EBVpositive and five out 46 EBV-negative patients (p = 0.01 at Fisher’s exact test). This finding was not found in OIND patients; it was also independent of the cell count in CSF, which was higher in OIND than in MS patients (p = 0.02 at Mann–Whitney U test), but was comparable between EBV-positive and EBV-negative MS patients. Thus, the relationship between lesion size and EBV-positive PCR seems not to reflect a non-specific recruitment of leucocytes in the central nervous system in the context of amplified inflammation. The increased chance of detecting EBV DNA in MS patients with more active lesions is instead in accord with Jacobson’s group’s finding1 (at least as far as EBV is concerned) and supports evidence of intrathecal reactivation and virus-driven immunopathogenic response in MS.2,3

BepiPred-2.0: Improving sequence-based B-cell epitope prediction using conformational epitopes

Abstract: Antibodies have become an indispensable tool for many biotechnological and clinical applications. They bind their molecular target (antigen) by recognizing a portion of its structure (epitope) in a highly specific manner. The ability to predict epitopes from antigen sequences alone is a complex task. Despite substantial effort, limited advancement has been achieved over the last decade in the accuracy of epitope prediction methods, especially for those that rely on the sequence of the antigen only. Here, we present BepiPred-2.0 (http://www.cbs.dtu.dk/services/BepiPred/), a web server for predicting B-cell epitopes from antigen sequences. BepiPred-2.0 is based on a random forest algorithm trained on epitopes annotated from antibody-antigen protein structures. This new method was found to outperform other available tools for sequence-based epitope prediction both on epitope data derived from solved 3D structures, and on a large collection of linear epitopes downloaded from the IEDB database. The method displays results in a user-friendly and informative way, both for computer-savvy and non-expert users. We believe that BepiPred-2.0 will be a valuable tool for the bioinformatics and immunology community.

Clinically isolated syndromes

Abstract: Summary Clinically isolated syndrome (CIS) is a term that describes a first clinical episode with features suggestive of multiple sclerosis (MS). It usually occurs in young adults and affects optic nerves, the brainstem, or the spinal cord. Although patients usually recover from their presenting episode, CIS is often the first manifestation of MS. The most notable risk factors for MS are clinically silent MRI lesions and CSF oligoclonal bands; weak or uncertain risk factors include vitamin D deficiency, Epstein-Barr virus infection, smoking, HLA genes, and miscellaneous immunological abnormalities. Diagnostic investigations including MRI aim to exclude alternative causes and to define the risk for MS. MRI findings incorporated into diagnostic criteria in the past decade enable MS to be diagnosed at or soon after CIS presentation. The course of MS after CIS is variable: after 15–20 years, a third of patients have a benign course with minimal or no disability and a half will have developed secondary progressive MS with increasing disability. Prediction of the long-term course at disease onset is unreliable. Disease-modifying treatments delay the development from CIS to MS. Their use in CIS is limited by uncertain long-term clinical prognosis and treatment benefits and adverse effects, although they have the potential to prevent or delay future tissue damage, including demyelination and axonal loss. Targets for future therapeutic progress are to achieve safe and effective long-term immunomodulation with neuroprotection and repair.

Green synthesis of metal and metal oxide nanoparticles from plant leaf extracts and their applications: A review

Abstract: Abstract Metal nanoparticles (MNPs) and metal oxide nanoparticles (MONPs) are used in numerous fields. The new nano-based entities are being strongly generated and incorporated into everyday personal care products, cosmetics, medicines, drug delivery, and clothing to impact industrial and manufacturing sectors, which means that nanomaterials commercialization and nano-assisted device will continuously grow. They can be prepared by many methods such as green synthesis and the conventional chemical synthesis methods. Green synthesis includes infinite accession to produce MNPs and MONPs with demanding properties. The structure–function relationships between nanomaterials and key information for life cycle evaluation lead to the production of high execution nanoscale materials that are gentle and environmentally friendly. Majority of plants have features as sustainable and renewable suppliers compared with microbes and enzymes, as they have the ability to pick up almost 75% of the light energy and transform it into chemical energy, contain chemicals like antioxidants and sugars, and play fundamental roles in the manufacture of nanoparticles. Plants considered the main factory for the green synthesis of MNPs and MONPs, and until now, different plant species have been used to study this, but the determined conditions should be taken into consideration to execute this preparation. In this study, we focus on the biosynthesis procedures to synthesize MNPs and MONPs, including comparison between green synthesis and the classical chemistry methods as well as the several new orientation of green synthesis of nanoparticles from different plant parts, especially plant leaf extracts. Plants with reducing compounds is the preferred choice for the synthesis of noble metals – metal ions can be reduced to the corresponding metals in the absence of any other chemicals under microwave irradiation conditions using benign solvent, water. Noble metals such as gold (Au), silver (Ag), platinum (Pt), and palladium (Pd) and other metals such as copper (Cu) and nickel (Ni), which are characterized by their optical, electronic, mechanical, magnetic, and chemical properties, leading to different technological applications. Plants with numerous reducing agents are suitable candidates for the manufacture of noble MNPs. The main purpose of this research is to give a background on green nanotechnology prospective evolution, pertinent concerns appeared related to the green synthesis of metal and metal oxide from plant extracts, nanoparticle formation mechanism, and the importance of flavonoids, vitamin B2, ascorbic acid (vitamin C), and phenolic compounds in the MNP and MONP production. The traditional sorghum beers are produced in many countries in Africa, but diversity in the production process may depend on the geographic localization. These beers are very rich in calories; B-group vitamins including thiamine, folic acid, riboflavin, and nicotinic acid; and essential amino acids such as lysine. However, the Western beers are more attractive than the traditional sorghum beers. The traditional sorghum beers have poor hygienic quality, organoleptic variations, and shorter shelf life compared with the Western beers. Many research studies on traditional sorghum beers have been carried out and documented in several African countries, especially the microbiological and biochemical properties, the technologies used in the manufacture processes, and synthetic characteristics of African traditional sorghum beers (ikigage, merissa, doro, dolo, pito, amgba, and tchoukoutou). The excellent resources for the production of greener biomaterials are plants and considerable advances have been achieved in many fields such as biotechnology and gene transfer. The manufactured biological nanomaterials have a great application in the pharmaceutical industry such as novel pharmaceuticals preparation, drug delivery personification procedures, and production of functional nanodevices.

Glycyrrhizic Acid in the Treatment of Liver Diseases: Literature Review

Abstract: Glycyrrhizic acid (GA) is a triterpene glycoside found in the roots of licorice plants (Glycyrrhiza glabra). GA is the most important active ingredient in the licorice root, and possesses a wide range of pharmacological and biological activities. GA coupled with glycyrrhetinic acid and 18-beta-glycyrrhetic acid was developed in China or Japan as an anti-inflammatory, antiviral, and antiallergic drug for liver disease. This review summarizes the current biological activities of GA and its medical applications in liver diseases. The pharmacological actions of GA include inhibition of hepatic apoptosis and necrosis; anti-inflammatory and immune regulatory actions; antiviral effects; and antitumor effects. This paper will be a useful reference for physicians and biologists researching GA and will open the door to novel agents in drug discovery and development from Chinese herbs. With additional research, GA may be more widely used in the treatment of liver diseases or other conditions.