@article {7695, title = {Pediatric patients with inflammatory bowel disease exhibit increased serum levels of proinflammatory cytokines and chemokines, but decreased circulating levels of macrophage inhibitory protein-1β, interleukin-2 and interleukin-17.}, journal = {Exp Ther Med}, volume = {9}, year = {2015}, month = {2015 Jun}, pages = {2047-2052}, abstract = {

Inflammatory bowel disease (IBD) is a chronic and progressive inflammatory condition of the gastrointestinal tract. Although the causative events that lead to the onset of IBD are yet to be fully elucidated, deregulation of immune and inflammatory mechanisms are hypothesized to significantly contribute to this disorder. Since the onset of IBD is often during infancy, in the present study, the serum values of a large panel of cytokines and chemokines in pediatric patients (<18 years; n=26) were compared with age-matched controls (n=37). While elevations in the serum level of several proinflammatory and immune regulating cytokines were confirmed, such as interleukin (IL)-1β, IL-5, IL-7, interferon (IFN)-γ-inducible protein-10, IL-16, cutaneous T-cell-attracting chemokine, leukemia inhibitory factor, monokine induced by γ-IFN, IFN-α2 and IFN-γ, notably decreased levels of IL-2, IL-17 and macrophage inhibitory protein-1β were also observed. Therefore, while a number of proinflammatory cytokines exhibit increased levels in IBD patients, pediatric IBD patients may also exhibit certain aspects of a reduced immunological response.

}, issn = {1792-0981}, doi = {10.3892/etm.2015.2370}, author = {Kleiner, Giulio and Zanin, Valentina and Monasta, Lorenzo and Crovella, Sergio and Caruso, Lorenzo and Milani, Daniela and Marcuzzi, Annalisa} } @article {3627, title = {Curcumin and inflammatory bowel disease: potential and limits of innovative treatments.}, journal = {Molecules}, volume = {19}, year = {2014}, month = {2014}, pages = {21127-53}, abstract = {

Curcumin belongs to the family of natural compounds collectively called curcuminoids and it possesses remarkable beneficial anti-oxidant, anti-inflammatory, anti-cancer, and neuroprotective properties. Moreover it is commonly assumed that curcumin has also been suggested as a remedy for digestive diseases such as inflammatory bowel diseases (IBD), a chronic immune disorder affecting the gastrointestinal tract and that can be divided in two major subgroups: Crohn{\textquoteright}s disease (CD) and Ulcerative Colitis (UC), depending mainly on the intestine tract affected by the inflammatory events. The chronic and intermittent nature of IBD imposes, where applicable, long-term treatments conducted in most of the cases combining different types of drugs. In more severe cases and where there has been no good response to the drugs, a surgery therapy is carried out. Currently, IBD-pharmacological treatments are generally not curative and often present serious side effects; for this reason, being known the relationship between nutrition and IBD, it is worthy of interesting the study and the development of new dietary strategy. The curcumin principal mechanism is the suppression of IBD inflammatory compounds (NF-κB) modulating immune response. This review summarizes literature data of curcumin as anti-inflammatory and anti-oxidant in IBD, trying to understand the different effects in CD e UC.

}, keywords = {Animals, Anti-Inflammatory Agents, Non-Steroidal, Chemistry, Pharmaceutical, Clinical Trials as Topic, Curcumin, Humans, Inflammatory Bowel Diseases, Molecular Targeted Therapy, Nanotechnology, Treatment Outcome}, issn = {1420-3049}, doi = {10.3390/molecules191221127}, author = {Vecchi Brumatti, Liza and Marcuzzi, Annalisa and Tricarico, Paola Maura and Zanin, Valentina and Girardelli, Martina and Bianco, Anna Monica} } @article {1961, title = {Family history in early-onset inflammatory bowel disease.}, journal = {J Gastroenterol}, volume = {48}, year = {2013}, month = {2013 Jan}, pages = {144}, keywords = {Colitis, Ulcerative, Crohn Disease, Female, Humans, Male}, issn = {1435-5922}, doi = {10.1007/s00535-012-0654-4}, author = {Bianco, Anna Monica and Zanin, Valentina and Monasta, Lorenzo and Martelossi, Stefano and Marcuzzi, Annalisa and Crovella, Sergio} } @article {1904, title = {Clarification of the pleiotropic effects of statins on mevalonate pathway and the feedback regulation of isoprenoids requires more comprehensive investigation.}, journal = {Cell Biochem Funct}, volume = {30}, year = {2012}, month = {2012 Mar}, pages = {176}, keywords = {Carcinoma, Hepatocellular, Enzyme Inhibitors, Humans, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Liver Neoplasms, Simvastatin, Terpenes}, issn = {1099-0844}, doi = {10.1002/cbf.2798}, author = {Bianco, Anna Monica and Zanin, Valentina and Marcuzzi, Annalisa and Crovella, Sergio} } @article {1842, title = {Comments to the editor concerning the paper entitled "Preclinical renal cancer chemopreventive efficacy of geraniol by modulation of multiple molecular pathways" Shiekh Tanveer Ahmad et al.}, journal = {Toxicology}, volume = {293}, year = {2012}, month = {2012 Mar 11}, pages = {123-4}, keywords = {Animals, Antineoplastic Agents, Kidney Neoplasms, Male, Signal Transduction, Terpenes}, issn = {1879-3185}, doi = {10.1016/j.tox.2011.12.008}, author = {Vuch, Josef and Marcuzzi, Annalisa and Zanin, Valentina and Crovella, Sergio} } @article {1864, title = {A common genetic background could explain early-onset Crohn{\textquoteright}s disease.}, journal = {Med Hypotheses}, volume = {78}, year = {2012}, month = {2012 Apr}, pages = {520-2}, abstract = {

Crohn{\textquoteright}s disease (CD) is a multifactorial disease, in which environmental, microbial and genetic factors play important roles. CD is characterized by a chronic granulomatous inflammation by necrotic scarring with aspects of full-thickness wall. In spite of affecting mainly young adults, sometimes, CD can be present in the first year of life (early onset Crohn disease, EOCD) showing an unpredictable course and being often more severe than at older ages. In this paper we propose the hypothesis that EOCD patients should be analyzed using a Mendelian approach with family studies aimed to identify new loci directly involved in the early onset Crohn{\textquoteright}s disease. So we will leave the classic association study approach used until now for the identification of genes responsible for susceptibility to CD and propose linkage family analysis as alternative and powerful tool for the identification of new genetic variants associated with familiar cases of EOCD.

}, keywords = {Crohn Disease, Genetic Linkage, Genetic Predisposition to Disease, Humans, Models, Biological}, issn = {1532-2777}, doi = {10.1016/j.mehy.2012.01.023}, author = {Bianco, Anna Monica and Zanin, Valentina and Girardelli, Martina and Magnolato, Andrea and Martelossi, Stefano and Martellossi, Stefano and Tommasini, Alberto and Marcuzzi, Annalisa and Crovella, Sergio} } @article {1898, title = {DEFB1 gene 5{\textquoteright} untranslated region (UTR) polymorphisms in inflammatory bowel diseases.}, journal = {Clinics (Sao Paulo)}, volume = {67}, year = {2012}, month = {2012}, pages = {395-8}, keywords = {5{\textquoteright} Untranslated Regions, Adult, Antimicrobial Cationic Peptides, beta-Defensins, Case-Control Studies, Colitis, Ulcerative, Crohn Disease, Female, Genetic Predisposition to Disease, Haplotypes, Humans, Inflammatory Bowel Diseases, Male, Polymorphism, Genetic, Polymorphism, Single Nucleotide}, issn = {1980-5322}, author = {Zanin, Valentina and Segat, Ludovica and Bianco, Anna Monica and Padovan, Lara and Tavares, Nathalia de Alencar Cunha and Crovella, Sergio} } @article {1955, title = {The effect of clodronate on a mevalonate kinase deficiency cellular model.}, journal = {Inflamm Res}, volume = {61}, year = {2012}, month = {2012 Dec}, pages = {1363-7}, abstract = {

BACKGROUND: A potential anti-inflammatory effect of clodronate--an aminobisphosphonate--was described to antagonize the pro-inflammatory effects of the block in the mevalonate pathway, the main feature of a rare auto-inflammatory disease called mevalonate kinase deficiency (MKD).

OBJECTIVE: In this study we evaluated the potential anti-inflammatory effect of clodronate in MKD--a still orphan drug pediatric disease.

METHODS: We studied some biological parameters, nitric oxide production using Griess reagents and programmed cell death by flow cytometry, as common inflammatory parameters in MKD, in the presence of different doses of clodronate (1, 10 and 100 μM).

RESULTS: In our cellular model and in monocytes from patients with MKD, clodronate induced an increase in programed cell death and nitric oxide production in comparison with non-treated cells.

CONCLUSION: Our findings suggest that clodronate does not have an anti-inflammatory effect as previously reported but that it increases the epiphenomena of this pediatric disease.

}, keywords = {Adolescent, Adult, Alendronate, Animals, Anti-Inflammatory Agents, Apoptosis, Cell Line, Cells, Cultured, Child, Clodronic Acid, Female, Humans, Inflammation, Lipopolysaccharides, Male, Mevalonate Kinase Deficiency, Mice, Models, Biological, Monocytes, Nitric Oxide, Young Adult}, issn = {1420-908X}, doi = {10.1007/s00011-012-0537-4}, author = {Zanin, Valentina and Marcuzzi, Annalisa and Piscianz, Elisa and Vuch, Josef and Bianco, Anna Monica and Monasta, Lorenzo and Decorti, Giuliana and Crovella, Sergio} } @article {1943, title = {Lovastatin-induced apoptosis is modulated by geranylgeraniol in a neuroblastoma cell line.}, journal = {Int J Dev Neurosci}, volume = {30}, year = {2012}, month = {2012 Oct}, pages = {451-6}, abstract = {

Mevalonic aciduria (MA), the most severe form of mevalonate kinase deficiency (MKD), is still an orphan drug disease and the pathogenetic mechanisms underlying neuronal dysfunction is still poorly understood. In our study we have investigated the apoptotic mechanism mediated by the exposure of the cultured neuroblastoma cell line, SH-SY5Y, to lovastatin in absence or in presence of the isoprenoid, geranylgeraniol, with the aim of unraveling the pathogenesis of MA. Lovastatin, blocks the mevalonate pathway inhibiting the 3-hydroxy-3-methylglutaryl-CoA reductase (HMG-CR), an enzyme of the mevalonate pathway upstream the mevalonate kinase enzyme, reproducing biochemical features similar to those found in MKD. We demonstrate that apoptosis in neuronal lovastatin treated-cells is induced by the mitochondrial pathway, with caspase-9 as the initiator and caspase-3 as the effector caspase. The presence of geranylgeraniol modulates both the caspase-9 and caspase-3 activity in a dose-dependent way, confirming that this isoprenoid enters the mevalonate pathway, is metabolized and finally is able to by-pass the statin biochemical block reconstituting the mevalonate pathway. According to our findings, it should not be the time course adopted that modulates the apoptotic response but rather the isoprenoid itself. Being aware that our results have been obtained using a biochemical model of MKD, and not cells from patients with the disease, we believe our findings increase the knowledge of MA pathogenesis, and may possibly contribute to the development of novel therapeutic strategies.

}, keywords = {Analysis of Variance, Apoptosis, Caspases, Cell Line, Tumor, Diterpenes, Dose-Response Relationship, Drug, Drug Interactions, Humans, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Lovastatin, Neuroblastoma, Time Factors}, issn = {1873-474X}, doi = {10.1016/j.ijdevneu.2012.06.002}, author = {Marcuzzi, Annalisa and Zanin, Valentina and Piscianz, Elisa and Tricarico, Paola Maura and Vuch, Josef and Girardelli, Martina and Monasta, Lorenzo and Bianco, Anna Monica and Crovella, Sergio} } @article {1963, title = {Polymorphisms in DC-SIGN and L-SIGN genes are associated with HIV-1 vertical transmission in a Northeastern Brazilian population.}, journal = {Hum Immunol}, volume = {73}, year = {2012}, month = {2012 Nov}, pages = {1159-65}, abstract = {

DC-SIGN and L-SIGN are receptors expressed on specialized macrophages in decidua, (Hofbauer and placental capillary endothelial cells), known to interact with several pathogens, including HIV-1. To disclose the possible involvement of these molecules in the susceptibility to HIV vertical transmission, we analyzed DC-SIGN and L-SIGN gene single nucleotide polymorphisms (SNPs) in 192 HIV-1 positive children and 58 HIV-1 negative children all born to HIV-1 positive mothers, as well as 96 healthy uninfected children not exposed to HIV-1, all from Northeast Brazil. The frequency of three SNPs in the DC-SIGN promoter (-139G>A, -201G>T and -336A>G) were significantly different when comparing HIV positive children with HIV-1 exposed uninfected children, indicating an association with susceptibility to HIV-1 vertical transmission. This genetic association suggests that DC-SIGN molecule may play a role in susceptibility to HIV-1 infection through vertical transmission.

}, keywords = {Alleles, Brazil, Cell Adhesion Molecules, Child, Child, Preschool, Exons, Female, Gene Frequency, Genotype, HIV Infections, HIV-1, Humans, Infectious Disease Transmission, Vertical, Lectins, C-Type, Male, Polymorphism, Single Nucleotide, Promoter Regions, Genetic, Receptors, Cell Surface, Tandem Repeat Sequences}, issn = {1879-1166}, doi = {10.1016/j.humimm.2012.07.338}, author = {da Silva, Ronaldo Celerino and Segat, Ludovica and Zanin, Valentina and Arraes, Luiz Claudio and Crovella, Sergio} } @article {1914, title = {Serum amyloid A and cholesterol: a pivotal role on inflammation.}, journal = {Amyloid}, volume = {19}, year = {2012}, month = {2012 Sep}, pages = {163-4; author reply 165-6}, keywords = {Animals, Humans, Serum Amyloid A Protein}, issn = {1744-2818}, doi = {10.3109/13506129.2012.689266}, author = {Tricarico, Paola Maura and Marcuzzi, Annalisa and Zanin, Valentina and Kleiner, Giulio and Bianco, Anna Monica and Crovella, Sergio} } @article {1909, title = {Specific protein profile in cerebrospinal fluid from HIV-1-positive cART-treated patients affected by neurological disorders.}, journal = {J Neurovirol}, volume = {18}, year = {2012}, month = {2012 Oct}, pages = {416-22}, abstract = {

Cytokines/chemokines are involved in the immune response of infections, including HIV-1. We defined the profile of 48 cytokines/chemokines in cerebrospinal fluid from 18 cART patients with chronic HIV-1 infection by Luminex technology. Nine patients were affected with leukoencephalopathies: five with John Cunningham virus (JCV) + progressive multifocal leukoencephalopathy (PML) and four with JCV-not determined leukoencephalopathy (NDLE). In addition, nine HIV-1-positive patients with no neurological signs (NND) and five HIV-1-negative patients affected with acute disseminated encephalomyelitis (ADEM) were enrolled. Ten cytokines (IL-15, IL-3, IL-16, IL-18, CTACK, GRO1, SCF, MCP-1, MIF, SDF) were highly expressed in HIV-1-positive patients while IL-1Ra and IL-17 were present at a lower level. In addition, the levels of IL-17, IL-9, FGF-basic, MIP-1β, and MCP-1 were significantly higher (p < 0.05) in patients with neurological diseases (PML, NDLE, ADEM) with respect to NND. Focusing the attention to the cytokine profile in JCV + PML patients with respect to JCV-NDLE patients, only TNF-β was significantly downregulated (p < 0.05) in JCV + PML patients. This pilot study emphasized the role of immunoregulation in HIV-1-related neurological disorders during cART treatment.

}, keywords = {Adult, Aged, Anti-HIV Agents, Cytokines, Encephalomyelitis, Acute Disseminated, Female, HIV Infections, HIV-1, Humans, Leukoencephalopathy, Progressive Multifocal, Male, Middle Aged, Pilot Projects}, issn = {1538-2443}, doi = {10.1007/s13365-012-0109-y}, author = {Zanin, Valentina and Delbue, Serena and Marcuzzi, Annalisa and Tavazzi, Eleonora and Del Savio, Rossella and Crovella, Sergio and Marchioni, Enrico and Ferrante, Pasquale and Comar, Manola} } @article {1600, title = {Comments on {\textquoteright}{\textquoteright}Geranylgeraniol--a new potential therapeutic approach to bisphosphonate associated osteonecrosis of the jaw" by Ziebart T et al. (2011).}, journal = {Oral Oncol}, volume = {47}, year = {2011}, month = {2011 May}, pages = {436-7; author reply 438}, keywords = {Bone Density Conservation Agents, Diphosphonates, Diterpenes, Humans, Jaw Diseases, Osteonecrosis}, issn = {1879-0593}, doi = {10.1016/j.oraloncology.2011.02.017}, author = {Marcuzzi, Annalisa and Zanin, Valentina and Crovella, Sergio and Pontillo, Alessandra} } @article {1761, title = {Letter to the editor: acute effects of intravenous administration of pamidronate in patients with osteoporosis.}, journal = {J Korean Med Sci}, volume = {26}, year = {2011}, month = {2011 Jun}, pages = {848-9; author reply 850}, keywords = {Anti-Inflammatory Agents, Cytokines, Diphosphonates, Humans, Injections, Intravenous, Osteoporosis}, issn = {1598-6357}, doi = {10.3346/jkms.2011.26.6.848}, author = {Marcuzzi, Annalisa and Zanin, Valentina and Vuch, Josef and Pontillo, Alessandra and Crovella, Sergio} } @article {1701, title = {Beta defensin-1 gene (DEFB1) polymorphisms are not associated with atopic dermatitis in children and adolescents from northeast Brazil (Recife, Pernambuco).}, journal = {Int J Dermatol}, volume = {49}, year = {2010}, month = {2010 Jun}, pages = {653-7}, abstract = {

BACKGROUND: Atopic dermatitis (AD) is a common inflammatory skin disease resulting from the interplay between environmental, immunological and genetic factors. In our study, we investigated the role of three single nucleotide polymorphisms (SNPs) at 5{\textquoteright}-UTR of DEFB1 gene, encoding for the human beta defensin-1, on the susceptibility to develop AD in a group of Brazilian children and adolescents.

METHODS: Three SNPs, -20 G/A (rs11362), -44 C/G (rs1800972), and -52 G/A (rs1799946) at 5{\textquoteright}-UTR of DEFB1 gene were genotyped in two groups of children and adolescents, one affected by AD (96 subjects), the other healthy (191 individuals), from northeast Brazil.

RESULTS: -44 C/G frequencies were comparable between the two groups. The -20 GG genotype was more frequent in AD subjects than in healthy controls; the -52 GG, conversely, was more frequent in healthy controls than in AD. However, both these differences did not reach statistical significance. Also, association between SNPs and AD severity has been shown. The analysis of DEFB1 haplotypes did not highlight any association of the three SNPs with AD development or disease severity.

CONCLUSIONS: Our results seem to exclude a role for the -44 C/G DEFB1 SNPs on the pathogenesis and severity of AD, while for the -20 C/G and -52 G/A, even if not statistically significant, we evidenced a slight trend for susceptibility (-20 GG) and protection (-52 GG) for the development of AD. However, as controversial findings have been reported in the literature, the role of DEFB1 in the development of AD and in the severity of the phenotype deserves further investigation.

}, keywords = {Adolescent, beta-Defensins, Brazil, Child, Child, Preschool, Dermatitis, Atopic, Female, Gene Frequency, Genetic Predisposition to Disease, Haplotypes, Humans, Infant, Male, Polymorphism, Single Nucleotide, Risk Factors}, issn = {1365-4632}, doi = {10.1111/j.1365-4632.2009.04343.x}, author = {Segat, Ludovica and Guimar{\~a}es, Rafael L and Brand{\~a}o, Lucas A C and Rocha, Cintia R C and Zanin, Valentina and Trevisiol, Chiara and de Lima Filho, Jos{\'e} Luiz and Crovella, Sergio} }