@article {10757, title = {Antibodies reacting to mimotopes of Simian virus 40 large T antigen, the viral oncoprotein, in sera from children.}, journal = {J Cell Physiol}, volume = {234}, year = {2019}, month = {2019 Apr}, pages = {3170-3179}, abstract = {

Recent data indicate that the Simian virus 40 (SV40) infection appears to be transmitted in humans independently from early SV40-contaminated antipolio vaccines. Serum antibodies against SV40 large T antigen (Tag) were analyzed in children/adolescents and young adults. To investigate antibodies reacting to SV40 Tag antigens, serum samples ( n = 812) from children and young adults were analyzed by indirect ELISAs using specific SV40 Tag mimotopes. Mimotopes were synthetic peptides corresponding to SV40 Tag epitopes. In sera ( n = 412) from healthy children up to 17 years old, IgG antibodies against SV40 Tag mimotopes reached an overall prevalence of 15\%. IgM antibodies against SV40 Tag were detected in sera of children 6-8 months old confirming and extending the knowledge that SV40 seroconversion occurs early in life. In children/adolescents affected by different diseases ( n = 180) SV40 Tag had a prevalence of 18\%, being the difference no significant compared to healthy subjects ( n = 220; 16\%) of the same age. Our immunological data indicate that SV40 circulates in children and young adults, both in healthy conditions and affected by distinct diseases. The IgM detection in sera from healthy children suggests that the SV40 infection/seroconversion occurs early in life (>6 months). Our immunological data support the hypothesis that SV40, or a closely related still unknown polyomavirus, infects humans. The SV40 seroprevalence is lower than common polyomaviruses, such as BKPyV and JCPyV, and other new human polyomaviruses. In addition, our immunological surveillance indicates a lack of association between different diseases, considered herein, and SV40.

}, issn = {1097-4652}, doi = {10.1002/jcp.27490}, author = {Mazzoni, Elisa and Frontini, Francesca and Rotondo, John Charles and Zanotta, Nunzia and Fioravanti, Arianna and Minelli, Francesca and Torreggiani, Elena and Campisciano, Giuseppina and Marcuzzi, Annalisa and Guerra, Giovanni and Tommasini, Alberto and Touz{\'e}, Antoine and Martini, Fernanda and Tognon, Mauro and Comar, Manola} } @article {10425, title = {Antibody response to polyomavirus primary infection: high seroprevalence of Merkel cell polyomavirus and lymphoid tissue involvement.}, journal = {J Neurovirol}, volume = {24}, year = {2018}, month = {2018 Jun}, pages = {314-322}, abstract = {

Human polyomaviruses (HPyVs) asymptomatically infect the human population establishing latency in the host, and their seroprevalence can reach 90\% in healthy adults. Few studies have focused on the pediatric population, and there are no reports regarding the seroprevalence of all the newly isolated HPyVs among Italian children. Therefore, we investigated the frequency of serum antibodies against 12 PyVs in 182 immunocompetent children from Northeast Italy, by means of a multiplex antibody detection system. Additionally, secondary lymphoid tissues were collected to analyze the presence of HPyV DNA sequences using a specific real-time PCRs or PCRs. Almost 100\% of subjects were seropositive for at least one PyV. Seropositivity ranged from 3\% for antibodies against simian virus 40 (SV40) in children from 0 to 3~years, to 91\% for antibodies against WU polyomavirus (WUPyV) and HPyV10 in children from 8 to 17~years. The mean number of PyV for which children were seropositive increased with the increasing of age: 4 standard deviations (SD) 1.8 in the 0-3-year group, 5 (SD 1.9) in the 4-7-year group, and 6 (SD 2.2) in the 8-17-year group. JC polyomavirus (JCPyV) DNA was detected in 1\% of the adenoids, WUPyV in 12\% of the tonsils, and 28\% of the adenoids, and Merkel cell polyomavirus (MCPyV) was present in 6 and 2\% of the tonsils and adenoids, respectively. Our study gives new insights on the serological evidence of exposure to PyVs during childhood, and on their possible respiratory route of transmission.

}, issn = {1538-2443}, doi = {10.1007/s13365-017-0612-2}, author = {Cason, Carolina and Monasta, Lorenzo and Zanotta, Nunzia and Campisciano, Giuseppina and Maestri, Iva and Tommasino, Massimo and Pawlita, Michael and Villani, Sonia and Comar, Manola and Delbue, Serena} } @article {10438, title = {Bariatric surgery drives major rearrangements of the intestinal microbiota including the biofilm composition.}, journal = {Front Biosci (Elite Ed)}, volume = {10}, year = {2018}, month = {2018 06 01}, pages = {495-505}, abstract = {

The intestinal microbiota disequilibrium has been associated with obesity, while the role of the gut mucosal biofilms in this pathology is still unknown. We analysed the changes in the intestinal microbiota of obese patients after bariatric surgery with the aim of disclosing the rearrangement of the biofilm configuration. Although the bariatric surgery drives major rearrangements of the gut microbiota, obese patients maintain the enterotype before and after surgery, as shown by normal weight patients, with an increase of and . The enterotype guarantees the strong ability to form a biofilm which allows a more efficient digestion of polysaccharides than planktonic communities and leads to the production of acetate which is a key player to inhibit enteropathogens. Additionally, the laparoscopic gastric bypass induces an increase of , a facultative anaerobic bacterium involved in intestinal and inflammatory disorders. Bariatric surgery influences the microbial composition of gut biofilm. Further studies are needed to elucidate the impact of this variation on recovery after surgery and on weight loss.

}, keywords = {Biofilms, Case-Control Studies, Gastric Bypass, Gastrointestinal Microbiome, Humans, Intestinal Mucosa, Obesity, Prospective Studies}, issn = {1945-0508}, author = {Campisciano, Giuseppina and Cason, Carolina and Palmisano, Silvia and Giuricin, Michela and Rizzardi, Alessia and Croce, Lory Saveria and De Manzini, Nicolo and Comar, Manola} } @article {10445, title = {Cytokine profiles of women with vulvodynia: Identification of a panel of pro-inflammatory molecular targets.}, journal = {Eur J Obstet Gynecol Reprod Biol}, volume = {226}, year = {2018}, month = {2018 Jul}, pages = {66-70}, abstract = {

OBJECTIVE: The vulvar pain syndrome (VPS) is a multifactorial disease severely influencing the lifestyle of affected women. Among possible etiological factors, local injury, peripheral and/or central sensitization of the nervous system, and a chronic inflammatory status have been positively associated with the development of VPS. The identification of a constitutive altered local inflammatory profile in VPS women may represent an important point in the characterization of patients{\textquoteright} phenotype as a useful marker influencing the vulvar micro-environment. The aim of this study was to investigative the possible role of the local cytokines production in women with VPS in comparison to healthy women.

STUDY DESIGN: In this study were collected vaginal swabs from 57 healthy women (HC) who never suffered from VPS and from 30 patients diagnosed with vulvodynia (VPS) by at least 3 years and currently symptomatic. All patients included in this study showed the absence of Sexually Transmitted (STD) diseases and Reproductive Tract Infection. Real-time PCR was performed to assess the genomic sequences of ST pathogens. The Luminex Bio-Plex platform was used for the analysis of a panel of 48 immune factors.

RESULTS: Eleven molecules, specifically involved in the pro-inflammatory pathway were significantly modulated in VPS patients in comparison to healthy women, suggesting a persistent inflammatory process.

CONCLUSIONS: Therefore, these inflammatory factors could be possible biological markers involved in this disease. Nevertheless, other studies are needed to consider this specific immune profile as a valid marker of the vulvodynia.

}, keywords = {Adult, Aged, Cytokines, Female, Humans, Inflammation, Middle Aged, Vaginal Smears, Vulva, Vulvodynia, Women{\textquoteright}s Health}, issn = {1872-7654}, doi = {10.1016/j.ejogrb.2018.05.035}, author = {Zanotta, Nunzia and Campisciano, Giuseppina and Scrimin, Federica and Blendi, Ura and Marcuzzi, Annalisa and Vincenti, Ezio and Crovella, Sergio and Comar, Manola} } @article {10782, title = {Fractional CO laser for genitourinary syndrome of menopause in breast cancer survivors: clinical, immunological, and microbiological aspects.}, journal = {Lasers Med Sci}, volume = {33}, year = {2018}, month = {2018 Jul}, pages = {1047-1054}, abstract = {

The composition of vaginal microbiome in menopause and cancer survivor women changes dramatically leading to genitourinary syndrome of menopause (GSM) in up to 70\% of patients. Recent reports suggest that laser therapy may be valuable as a not hormonal therapeutic modality. The aim of the present study was to evaluate the effects of fractional CO laser treatment on the vaginal secretory pathway of a large panel of immune mediators, usually implicated in tissue remodeling and inflammation, and on microbiome composition in postmenopausal breast cancer survivors. The Ion Torrent PGM platform and the Luminex Bio-Plex platform were used for microbiome and immune factor analysis. The significant reduction of clinical symptoms and the non-significant changes in vaginal microbiome support the efficacy and safety of laser treatment. Moreover, the high remodeling status in vaginal epithelium is demonstrated by the significant changes in inflammatory and modulatory cytokine patterns. Laser therapy can be used for the treatment of GSM symptoms and does not show any adverse effects. However, further studies will be needed to clarify its long-term efficacy and other effects.

}, keywords = {Breast Neoplasms, Cancer Survivors, Cytokines, Dyspareunia, Female, Humans, Lasers, Gas, Menopause, Microbiota, Middle Aged, Prospective Studies, Syndrome, Vagina, Vaginal Diseases}, issn = {1435-604X}, doi = {10.1007/s10103-018-2471-3}, author = {Becorpi, Angelamaria and Campisciano, Giuseppina and Zanotta, Nunzia and Tredici, Zelinda and Guaschino, Secondo and Petraglia, Felice and Pieralli, Annalisa and Sisti, Giovanni and De Seta, Francesco and Comar, Manola} } @article {10799, title = {In vivo microbiome and associated immune markers: New insights into the pathogenesis of vaginal dysbiosis.}, journal = {Sci Rep}, volume = {8}, year = {2018}, month = {2018 02 02}, pages = {2307}, abstract = {

The microbiota fulfils a key role in the training and function of the immune system, which contributes to the symbiosis between the host and complex microbial communities. In this study, we characterized the interplay between vaginal bacteria and local immune mediators during dysbiosis in selected women of reproductive age who were grouped according to Nugent{\textquoteright}s criteria. The abundance of Gardnerella vaginalis and Bifidobacterium breve was increased in the intermediate dysbiotic status, while the presence of a plethora of non-resident bacteria characterized the group with overt vaginosis. In response to these increases, the anti-inflammatory IL1ra and pro-inflammatory IL2 increased, while the embryo trophic factors FGFβ and GMCSF decreased compared to the healthy milieu. A specific pattern, including IL1α, IL1β, IL8, MIG, MIP1α and RANTES, distinguished the intermediate group from the vaginosis group, while IL5 and IL13, which are secreted by Th2 cells, were significantly associated with the perturbation of the commensals Lactobacilli, Gardnerella and Ureaplasma. Summarizing, we postulate that although the dysbiotic condition triggers a pro-inflammatory process, the presence of a steady state level of Th2 may influence clinical manifestations. These results raise clinically relevant questions regarding the use of vaginal immunological markers as efficacious tools to monitor microbial alterations.

}, keywords = {Adult, Biomarkers, Cytokines, Dysbiosis, Female, Humans, Microbiota, Th2 Cells, Vagina}, issn = {2045-2322}, doi = {10.1038/s41598-018-20649-x}, author = {Campisciano, Giuseppina and Zanotta, Nunzia and Licastro, Danilo and De Seta, Francesco and Comar, Manola} } @article {10439, title = {Vaginal microbiota dysmicrobism and role of biofilm-forming bacteria.}, journal = {Front Biosci (Elite Ed)}, volume = {10}, year = {2018}, month = {2018 06 01}, pages = {528-536}, abstract = {

Bacterial vaginosis involves the presence of a polymicrobial biofilm on the vaginal epithelium, guaranteeing immune escape and spread of antibiotic resistance. To spot known biofilm-forming bacteria, we profiled the vaginal microbiome of sixty-four symptomatic women suffering from a different grade of vaginal disorders and sixty asymptomatic healthy women. Specific microbial profiles distinguished symptomatic from asymptomatic women and characterized the grade of dysmicrobism within the symptomatic group. Lactobacillus crispatus and iners predominated on the healthy vaginal mucosa, while Lactobacillus gasseri predominated in the intermediate dysmicrobism. Furthermore, the intermediate grade of dysmicrobism was characterized by other lactic acid-producers species than Lactobacilli, able to rescue the microbial imbalance, and Ureaplasma parvum-serovar 3. The vaginosis group exhibited the overgrowth of Prevotella bivia, which is known to enhance the biofilm formation by Gardnerella vaginalis, and the presence of Streptococcus anginosus, which is emerging as a new cooperating player of the vaginal biofilm. Identifying specific microorganisms promoting or preventing the biofilm formation could increase the accuracy for a better definition of the vaginal dysmicrobism concept and therapeutic intervention.

}, keywords = {Adult, Biofilms, Female, Humans, Microbiota, Vagina, Vaginosis, Bacterial}, issn = {1945-0508}, author = {Campisciano, Giuseppina and Zanotta, Nunzia and Petix, Vincenzo and Corich, Lucia and De Seta, Francesco and Comar, Manola} } @article {10485, title = {Shifts of subgingival bacterial population after nonsurgical and pharmacological therapy of localized aggressive periodontitis, followed for 1 year by Ion Torrent PGM platform.}, journal = {Eur J Dent}, volume = {11}, year = {2017}, month = {2017 Jan-Mar}, pages = {126-129}, abstract = {

The possibility of targeting the hypervariable region V3 of the 16S rRNA gene using Ion Torrent Personal Genome Machine (PGM) could provide a complete analysis of subgingival plaque samples, potentially able to identify microbiological species missed by culture-based methods. A 16-year-old female smoker patient, affected by localized aggressive periodontitis, underwent a full-mouth disinfection protocol and was inserted in a 3-month recall program. Microbiological samples were collected at baseline and at 30, 100, 365 days follow-up and analyzed by Ion Torrent PGM. , , , and were the most represented pathogens at baseline. Nonsurgical treatment and systemic antibiotics drastically lowered the anaerobic species, and their presence remained limited after 100 days, while a consistent recolonization by anaerobic bacteria was detected at 365 days. The patient showed a general improvement of periodontal conditions. Differently from polymerase chain reaction and other microarray techniques, Ion Torrent performs a quantitative analysis of the microbiota, irrespective of the searched species. An accurate definition of the shifts of the bacterial community might help periodontal researchers for a better understanding of the impact of different treatment approaches or in intercepting nonresponsive conditions.

}, issn = {1305-7456}, doi = {10.4103/ejd.ejd_309_16}, author = {Campisciano, Giuseppina and Toschetti, Annamaria and Comar, Manola and Taranto, Rosanna Di and Berton, Federico and Stacchi, Claudio} } @article {10466, title = {Subclinical alteration of the cervical-vaginal microbiome in women with idiopathic infertility.}, journal = {J Cell Physiol}, volume = {232}, year = {2017}, month = {2017 Jul}, pages = {1681-1688}, abstract = {

Biomarkers have a wide application in research and clinic, they help to choose the correct treatment for diseases. Recent studies, addressing the vaginal microbiome using next generation sequencing (NGS), reported the involvement of bacterial species in infertility. We compared the vaginal microbiome of idiopathic infertile women with that of healthy, including bacterial vaginosis affected women and non-idiopathic infertile women, to identify bacterial species suitable as biomarkers. Information on microorganisms was obtained from the V3-16S rDNA sequencing of cervical-vaginal fluids of 96 women using the Ion Torrent platform. Data were processed with QIIME and classified against the Vaginal 16S rDNA Reference Database. The analysis revealed a significant beta-diversity variation (p < 0.001) between the four groups included in the study. L. iners, L. crispatus, and L. gasseri distinguished idiopathic infertile women from the other groups. In these women, a microbial profile similar to that observed in bacterial vaginosis women has been detected. Our results suggest that the quantitative assessment and identification of specific microorganisms of the cervical-vaginal microflora could increase the accuracy of available tools for the diagnosis of infertility and improve the adoption of therapeutic protocols.

}, keywords = {Adult, Biodiversity, Cervix Uteri, Cohort Studies, Demography, Female, Humans, Infertility, Female, Microbiota, Species Specificity, Vagina, Vaginosis, Bacterial}, issn = {1097-4652}, doi = {10.1002/jcp.25806}, author = {Campisciano, Giuseppina and Florian, Fiorella and D{\textquoteright}Eustacchio, Angela and Stankovi{\'c}, David and Ricci, Giuseppe and De Seta, Francesco and Comar, Manola} } @article {10571, title = {SV40 Infection of Mesenchymal Stromal Cells From Wharton{\textquoteright}s Jelly Drives the Production of Inflammatory and Tumoral Mediators.}, journal = {J Cell Physiol}, volume = {232}, year = {2017}, month = {2017 Nov}, pages = {3060-3066}, abstract = {

The Mesenchymal Stromal Cells from umbilical cord Wharton{\textquoteright}s jelly (WJSCs) are a source of cells with high potentiality for the treatment of human immunological disorders. Footprints of the oncogenic viruses Simian Virus 40 (SV40) and JC Virus (JCPyV) have been recently detected in human WJSCs specimens. The aim of this study is to evaluate if WJSCs can be efficiently infected by these Polyomaviruses and if they can potentially exert tumoral activity. Cell culture experiments indicated that WJSCs could sustain both SV40 and JCPyV infections. A transient and lytic replication was observed for JCPyV, while SV40 persistently infected WJSCs over a long period of time, releasing a viral progeny at low titer without evident cytopathic effect (CPE). Considering the association between SV40 and human tumors and the reported ability of the oncogenic viruses to drive the host innate immune response to cell transformation, the expression profile of a large panel of immune mediators was evaluated in supernatants by the Bioplex platform. RANTES, IL-3, MIG, and IL-12p40, involved in chronic inflammation, cells differentiation, and transformation, were constantly measured at high concentration comparing to control. These findings represent a new aspect of SV40 biological activity in the humans, highlighting its interaction with specific host cellular pathways. In view of these results, it seems to be increasingly urgent to consider Polyomaviruses in the management of WJSCs for their safely use as promising therapeutic source. J. Cell. Physiol. 232: 3060-3066, 2017. {\textcopyright} 2016 Wiley Periodicals, Inc.

}, keywords = {Cell Line, Transformed, Cell Separation, Cell Transformation, Viral, Chemokine CCL5, Chemokine CXCL9, Cytopathogenic Effect, Viral, DNA, Viral, Host-Pathogen Interactions, Humans, Inflammation Mediators, Interleukin-12 Subunit p40, Interleukin-3, JC Virus, Mesenchymal Stem Cells, Real-Time Polymerase Chain Reaction, Simian virus 40, Time Factors, Up-Regulation, Viral Load, Virus Replication, Wharton Jelly}, issn = {1097-4652}, doi = {10.1002/jcp.25723}, author = {Cason, Carolina and Campisciano, Giuseppina and Zanotta, Nunzia and Valencic, Erica and Delbue, Serena and Bella, Ramona and Comar, Manola} } @article {8314, title = {HPV genotypes distribution in Chlamydia trachomatis co-infection in a large cohort of women from north-east Italy.}, journal = {J Med Microbiol}, volume = {65}, year = {2016}, month = {2016 May}, pages = {406-13}, abstract = {

Human papillomavirus (HPV) and Chlamydia trachomatis are pathogens with oncogenic potential associated with persistent infections. Epidemiological data on C. trachomatis infection status, C. trachomatis/HPV co-infection and the relationship between HPV genotypes in Italian women are only preliminary. The aim of the present study was to characterize the relationship between HPV genotypes and C. trachomatis in an extending cohort of asymptomatic immunocompetent women from an area of north-east Italy. A retrospective study was conducted using Luminex technology on cervical swabs from asymptomatic immunocompetent women, comprising 921 attending the prevention centre for the Cervical Cancer Program and 6214 who had been referred to the Sexually Transmitted Infections Center, with clinical indications of HPV and C. trachomatis infections. A quantitative real-time PCR was performed to assess chronic C. trachomatis infection by heat-shock protein 60 (Hsp60) gene expression. The overall prevalence of the investigated pathogens was 39 \% (359/921) for HPV and 4 \% (251/6214) for C. trachomatis. The Hsp60 gene was detected in 57 \% of the women infected with C. trachomatis. HPV co-infection was present in 58 \% of C. trachomatis-infected women. A high prevalence of co-infection was found in women with chronic C. trachomatis infection (68 \%, P = 0.0002), especially in women <= 25 years (72 \%) where HPV multiple infections were found in 78 \% (P = 0.022). HPV genotype distribution showed that uncommon low-risk genotypes were associated with C. trachomatis. These results indicate a high frequency of co-detection of multiple HPV genotypes in chronically infected young women and suggest that the expression of the C. trachomatis Hsp60 gene may favour HPV infection.

}, issn = {1473-5644}, doi = {10.1099/jmm.0.000245}, author = {Seraceni, Silva and Campisciano, Giuseppina and Contini, Carlo and Comar, Manola} } @article {3518, title = {Block of the mevalonate pathway triggers oxidative and inflammatory molecular mechanisms modulated by exogenous isoprenoid compounds.}, journal = {Int J Mol Sci}, volume = {15}, year = {2014}, month = {2014}, pages = {6843-56}, abstract = {

Deregulation of the mevalonate pathway is known to be involved in a number of diseases that exhibit a systemic inflammatory phenotype and often neurological involvements, as seen in patients suffering from a rare disease called mevalonate kinase deficiency (MKD). One of the molecular mechanisms underlying this pathology could depend on the shortage of isoprenoid compounds and the subsequent mitochondrial damage, leading to oxidative stress and pro-inflammatory cytokines{\textquoteright} release. Moreover, it has been demonstrated that cellular death results from the balance between apoptosis and pyroptosis, both driven by mitochondrial damage and the molecular platform inflammasome. In order to rescue the deregulated pathway and decrease inflammatory markers, exogenous isoprenoid compounds were administered to a biochemical model of MKD obtained treating a murine monocytic cell line with a compound able to block the mevalonate pathway, plus an inflammatory stimulus. Our results show that isoprenoids acted in different ways, mainly increasing the expression of the evaluated markers [apoptosis, mitochondrial dysfunction, nucleotide-binding oligomerization-domain protein-like receptors 3 (NALP3), cytokines and nitric oxide (NO)]. Our findings confirm the hypothesis that inflammation is triggered, at least partially, by the shortage of isoprenoids. Moreover, although further studies are necessary, the achieved results suggest a possible role for exogenous isoprenoids in the treatment of MKD.

}, keywords = {Animals, Apoptosis, Carotenoids, Carrier Proteins, Cell Line, Cytokines, Diterpenes, Humans, Mevalonate Kinase Deficiency, Mevalonic Acid, Mice, Mitochondria, Nitric Oxide, Phytol, Terpenes}, issn = {1422-0067}, doi = {10.3390/ijms15046843}, author = {Tricarico, Paola Maura and Kleiner, Giulio and Valencic, Erica and Campisciano, Giuseppina and Girardelli, Martina and Crovella, Sergio and Knowles, Alessandra and Marcuzzi, Annalisa} }