Publications by authors named "M Scarpa"

553 Publications

Persistent Herpes Simplex Virus Type 1 Infection of Enteric Neurons Triggers CD8 T Cell Response and Gastrointestinal Neuromuscular Dysfunction.

Front Cell Infect Microbiol 2021 18;11:615350. Epub 2021 May 18.

Department of Molecular Medicine, University of Padova, Padova, Italy.

Behind the central nervous system, neurotropic viruses can reach and persist even in the enteric nervous system (ENS), the neuronal network embedded in the gut wall. We recently reported that immediately following orogastric (OG) administration, Herpes simplex virus (HSV)-1 infects murine enteric neurons and recruits mononuclear cells in the myenteric plexus. In the current work, we took those findings a step forward by investigating the persistence of HSV-1 in the ENS and the local adaptive immune responses against HSV-1 that might contribute to neuronal damage in an animal model. Our study demonstrated specific viral RNA transcripts and proteins in the longitudinal muscle layer containing the myenteric plexus (LMMP) up to 10 weeks post HSV-1 infection. CD3CD8INF╬│ lymphocytes skewed towards HSV-1 antigens infiltrated the myenteric ganglia starting from the 6 week of infection and persist up to 10 weeks post-OG HSV-1 inoculation. CD3CD8 cells isolated from the LMMP of the infected mice recognized HSV-1 antigens expressed by infected enteric neurons. , infiltrating activated lymphocytes were involved in controlling viral replication and intestinal neuromuscular dysfunction. Indeed, by depleting the CD8 cells by administering specific monoclonal antibody we observed a partial amelioration of intestinal dysmotility in HSV-1 infected mice but increased expression of viral genes. Our findings demonstrate that HSV-1 persistently infects enteric neurons that in turn express viral antigens, leading them to recruit activated CD3CD8 lymphocytes. The T-cell responses toward HSV-1 antigens persistently expressed in enteric neurons can alter the integrity of the ENS predisposing to neuromuscular dysfunction.
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http://dx.doi.org/10.3389/fcimb.2021.615350DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8169984PMC
May 2021

Accurate Molecular Diagnosis of Gaucher Disease Using Clinical Exome Sequencing as a First-Tier Test.

Int J Mol Sci 2021 May 24;22(11). Epub 2021 May 24.

Regional Coordinator Centre for Rare Diseases, University Hospital of Udine, 33100 Udine, Italy.

Gaucher disease (GD) is an autosomal recessive lysosomal disorder due to beta-glucosidase gene () mutations. The molecular diagnosis of GD is complicated by the presence of recombinant alleles originating from a highly homologous pseudogene. Clinical exome sequencing (CES) is a rapid genetic approach for identifying disease-causing mutations. However, copy number variation and recombination events are poorly detected, and further investigations are required to avoid mis-genotyping. The aim of this work was to set-up an integrated strategy for GD patients genotyping using CES as a first-line test. Eight patients diagnosed with GD were analyzed by CES. Five patients were fully genotyped, while three were revealed to be homozygous for mutations that were not confirmed in the parents. Therefore, MLPA (multiplex ligation-dependent probe amplification) and specific long-range PCR were performed, and two recombinant alleles, one of them novel, and one large deletion were identified. Furthermore, an MLPA assay performed in one family resulted in the identification of an additional novel mutation (p.M124V) in a relative, in trans with the known p.N409S mutation. In conclusion, even though CES has become extensively used in clinical practice, our study emphasizes the importance of a comprehensive molecular strategy to provide proper genotyping and genetic counseling.
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http://dx.doi.org/10.3390/ijms22115538DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8197298PMC
May 2021

Children's Preferences for Oral Dosage Forms and Their Involvement in Formulation Research via EPTRI (European Paediatric Translational Research Infrastructure).

Pharmaceutics 2021 May 15;13(5). Epub 2021 May 15.

Department of Pharmaceutics, University College London School of Pharmacy, 29-39 Brunswick Square, London WC1N 1AX, UK.

The paucity of evidence-based data on formulation characteristics preferred by the children is known to limit the design of tailored paediatric dosage forms. The European Paediatric Translational Research Infrastructure (EPTRI) commissioned a study to evaluate children's dosage forms perceived preferences in some European countries and explore the feasibility of using the young persons advisory groups (YPAGs) to involve children in formulation research. An online, age-adapted survey was developed and translated into six languages. The survey link was disseminated across seven European countries: Albania, Italy, the Netherlands, and Dutch-speaking part of Belgium, Romania, Spain, and the United Kingdom. Respondents' ( = 1172) perceived preferences for oral dosage forms primarily differed based on age, health status, and experience. Conventional dosage forms, i.e., liquid (35%), tablets (19%), and capsules (14%), were the most selected. Liquid was widely selected by children less than 12 years and by those healthy and taking medicines rarely. Monolithic solid forms were mostly chosen by adolescents and by children with a chronic disease taking medicines frequently. There was a clear lack of familiarity with more novel dosage forms (e.g., orodispersible films and granules). Noteworthy, granules were not appreciated, particularly by adolescents (52.8%). To rationalise the creation of paediatric formulations, it is important to involve children as active stakeholders and to apply tools assessing children's perspectives on medicines to inform acceptable dosage form development from the start.
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http://dx.doi.org/10.3390/pharmaceutics13050730DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8156390PMC
May 2021

Prevention Strategies for Esophageal Cancer-An Expert Review.

Cancers (Basel) 2021 May 1;13(9). Epub 2021 May 1.

Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy.

In the last 30 years, we have witnessed a rapid increase in the incidence and prevalence of esophageal cancer in many countries around the word. However, despite advancements in diagnostic technologies, the early detection of this cancer is rare, and its prognosis remains poor, with only about 20% of these patients surviving for 5 years. The two major forms are the esophageal squamous cell carcinoma (ESCC), which is particularly frequent in the so-called Asian belt, and the esophageal adenocarcinoma (EAC), which prevails in Western populations. This review provides a summary of the epidemiological features and risk factors associated with these tumors. Moreover, a major focus is posed on reporting and highlighting the various preventing strategies proposed by the most important international scientific societies, particularly in high-risk populations, with the final aim of detecting these lesions as early as possible and therefore favoring their definite cure. Indeed, we have conducted analysis with attention to the current primary, secondary and tertiary prevention guidelines in both ESCC and EAC, attempting to emphasize unresolved research and clinical problems related to these topics in order to improve our diagnostic strategies and management.
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http://dx.doi.org/10.3390/cancers13092183DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8125297PMC
May 2021

MLH1 Deficiency Down-Regulates TLR4 Expression in Sporadic Colorectal Cancer.

Front Mol Biosci 2021 7;8:624873. Epub 2021 May 7.

Clinica Chirurgica I, Azienda Ospedaliera di Padova, Padua, Italy.

Patients with mismatch repair (MMR)-deficient colorectal cancer (CRC) have a more favorable prognosis than patients with tumors with intact MMR. In order to obtain further insights on the reasons for this different outcome, we investigated the interplay between MMR genes and TLR4/MyD88 signaling. The cancer genome atlas (TCGA) databases were selected to predict the differential expression of TLR4 in colon cancer and its correlation with MMR genes. Moreover, the expression of MMR genes and TLR4 was evaluated by immunohistochemistry in 113 CRC samples and a cohort of 63 patients was used to assess mRNA expression and epigenetic silencing status. , the effect of knockdown on expression was quantified by Real Time PCR. TLR4 expression resulted dependent on MMR status and directly correlated to MLH1 expression. , silencing decreased expression. These observations may reflect the better prognosis and the chemoresistance of patients with CRC and MMR defects.
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http://dx.doi.org/10.3389/fmolb.2021.624873DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8139190PMC
May 2021