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Article ; Online: Management of nutritional consultations in local clinics during SARS-CoV-2 pandemic.

Accardi, Francesca / Cammarata, Isabella / Canaletti, Fulvia / Bachini, Ilaria / Demagistris, Anna

2020 Volume 69, Issue 3, Page(s) 438–440

MeSH term(s)	Humans ; SARS-CoV-2 ; Pandemics ; COVID-19
Keywords	covid19
Language	English
Publishing date	2020-06-02
Publishing country	Italy
Document type	Journal Article
ZDB-ID	3062713-8
ISSN	2724-5365
ISSN (online)	2724-5365
DOI	10.23736/S2724-5985.20.02716-6
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Article: Management of nutritional consultations in local clinics during SARS-CoV-2 pandemic

Accardi, Francesca / Cammarata, Isabella / Canaletti, Fulvia / Bachini, Ilaria / Demagistris, Anna

Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #32492996
Database	COVID19

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Article ; Online: Aflatoxin B1 and Epstein-Barr virus-induced CCL22 expression stimulates B cell infection.

Proceedings of the National Academy of Sciences of the United States of America

2024 Volume 121, Issue 16, Page(s) e2314426121

Abstract: Epstein-Barr Virus (EBV) infects more than 90% of the adult population worldwide. EBV infection is associated with Burkitt lymphoma (BL) though alone is not sufficient to induce carcinogenesis implying the involvement of co-factors. BL is endemic in ... ...

Abstract	Epstein-Barr Virus (EBV) infects more than 90% of the adult population worldwide. EBV infection is associated with Burkitt lymphoma (BL) though alone is not sufficient to induce carcinogenesis implying the involvement of co-factors. BL is endemic in African regions faced with mycotoxins exposure. Exposure to mycotoxins and oncogenic viruses has been shown to increase cancer risks partly through the deregulation of the immune response. A recent transcriptome profiling of B cells exposed to aflatoxin B1 (AFB1) revealed an upregulation of the Chemokine ligand 22 (CCL22) expression although the underlying mechanisms were not investigated. Here, we tested whether mycotoxins and EBV exposure may together contribute to endemic BL (eBL) carcinogenesis via immunomodulatory mechanisms involving CCL22. Our results revealed that B cells exposure to AFB1 and EBV synergistically stimulated CCL22 secretion via the activation of Nuclear Factor-kappa B pathway. By expressing EBV latent genes in B cells, we revealed that elevated levels of CCL22 result not only from the expression of the latent membrane protein LMP1 as previously reported but also from the expression of other viral latent genes. Importantly, CCL22 overexpression resulting from AFB1-exposure in vitro increased EBV infection through the activation of phosphoinositide-3-kinase pathway. Moreover, inhibiting CCL22 in vitro and in humanized mice in vivo limited EBV infection and decreased viral genes expression, supporting the notion that CCL22 overexpression plays an important role in B cell infection. These findings unravel new mechanisms that may underpin eBL development and identify novel pathways that can be targeted in drug development.
MeSH term(s)	Animals ; Mice ; Herpesvirus 4, Human/genetics ; Epstein-Barr Virus Infections/complications ; Aflatoxin B1/toxicity ; Ligands ; Burkitt Lymphoma/metabolism ; Chemokines ; Carcinogenesis
Chemical Substances	Aflatoxin B1 (9N2N2Y55MH) ; Ligands ; Chemokines
Language	English
Publishing date	2024-04-04
Publishing country	United States
Document type	Journal Article
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.2314426121
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Article ; Online: Intrabodies targeting human papillomavirus 16 E6 and E7 oncoproteins for therapy of established HPV-associated tumors.

Paolini, Francesca / Amici, Carla / Carosi, Mariantonia / Bonomo, Claudia / Di Bonito, Paola / Venuti, Aldo / Accardi, Luisa

Journal of experimental & clinical cancer research : CR

2021 Volume 40, Issue 1, Page(s) 37

Abstract: Background: The oncogenic activity of the high risk human papillomavirus type 16 (HPV16) is fully dependent on the E6 and E7 viral oncoproteins produced during viral infection. The oncoproteins interfere with cellular homeostasis by promoting ... ...

Abstract	Background: The oncogenic activity of the high risk human papillomavirus type 16 (HPV16) is fully dependent on the E6 and E7 viral oncoproteins produced during viral infection. The oncoproteins interfere with cellular homeostasis by promoting proliferation, inhibiting apoptosis and blocking epithelial differentiation, driving the infected cells towards neoplastic progression. The causal relationship between expression of E6/E7 and cellular transformation allows inhibiting the oncogenic process by hindering the activity of the two oncoproteins. We previously developed and characterized some antibodies in single-chain format (scFvs) against the HPV16 E6 and E7 proteins, and demonstrated both in vitro and in vivo their antitumor activity consisting of protective efficacy against tumor progression of HPV16-positive cells. Methods: Envisioning clinical application of the best characterized anti-HPV16 E6 and -HPV16 E7 scFvs, we verified their activity in the therapeutic setting, on already implanted tumors. Recombinant plasmids expressing the anti-HPV16 E6 scFvI7 with nuclear targeting sequence, or the anti-HPV16 E7 scFv43M2 with endoplasmic reticulum targeting sequence were delivered by injection followed by electroporation to three different preclinical models using C57/BL6 mice, and their effect on tumor growth was investigated. In the first model, the HPV16+ TC-1 Luc cells were used to implant tumors in mice, and tumor growth was measured by luciferase activity; in the second model, a fourfold number of TC-1 cells was used to obtain more aggressively growing tumors; in the third model, the HPV16+ C3 cells where used to rise tumors in mice. To highlight the scFv possible mechanism of action, H&E and caspase-3 staining of tumor section were performed. Results: We showed that both the anti-HPV16 E6 and HPV16 E7 scFvs tested were efficacious in delaying tumor progression in the three experimental models and that their antitumor activity seems to rely on driving tumor cells towards the apoptotic pathway. Conclusion: Based on our study, two scFvs have been identified that could represent a safe and effective treatment for the therapy of HPV16-associated lesions. The mechanism underlying the scFv effectiveness appears to be leading cells towards death by apoptosis. Furthermore, the validity of electroporation, a methodology allowed for human treatment, to deliver scFvs to tumors was confirmed.
MeSH term(s)	Animals ; Cell Line, Tumor ; Female ; Human papillomavirus 16/immunology ; Humans ; Mice ; Oncogene Proteins, Viral/immunology ; Papillomavirus E7 Proteins/immunology
Chemical Substances	Oncogene Proteins, Viral ; Papillomavirus E7 Proteins
Language	English
Publishing date	2021-01-23
Publishing country	England
Document type	Journal Article
ZDB-ID	803138-1
ISSN	1756-9966 ; 0392-9078
ISSN (online)	1756-9966
ISSN	0392-9078
DOI	10.1186/s13046-021-01841-w
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Article: Prevalence of 13 polyomaviruses in actinic keratosis and matched healthy skin samples of immunocompetent individuals.

Donà, Maria Gabriella / Gheit, Tarik / Chiantore, Maria Vincenza / Vescio, Maria Fenicia / Luzi, Fabiola / Rollo, Francesca / Accardi, Luisa / Cota, Carlo / Galati, Luisa / Romeo, Giovanna / Giuliani, Massimo / Tommasino, Massimo / Di Bonito, Paola

Infectious agents and cancer

2022 Volume 17, Issue 1, Page(s) 59

Abstract: Background: Actinic keratosis (AK) is a precursor of cutaneous squamous cell carcinoma (cSCC). UV radiation is the major risk factor for AK, but certain human papillomaviruses (HPVs) of the beta genus are also involved in its development. Differently, ... ...

Abstract	Background: Actinic keratosis (AK) is a precursor of cutaneous squamous cell carcinoma (cSCC). UV radiation is the major risk factor for AK, but certain human papillomaviruses (HPVs) of the beta genus are also involved in its development. Differently, the role of polyomaviruses (PyVs) in skin carcinogenesis is still debated. Fiftheen PyVs have been isolated from human tissues so far, including Merkel cell polyomavirus (MCPyV), the aetiological agent of Merkel cell carcinoma. Methods: The presence of 13 PyVs was assessed in skin samples from AK patients (n = 342). Matched fresh-frozen scrapings from healthy skin (HS) and AK lesions from 242 patients, and formalin-fixed paraffin-embedded AK biopsies from a different cohort of 100 patients were analyzed by multiplex PyVs genotyping assay. Results: The most frequent lesion site was the scalp in men (27.3%), and the cheek area in women (29.0%). Differences between men and women were significant for the scalp, the cheek area and the lips. Almost all the scrapings were PyV-positive (HS: 89.7%, AK: 94.6%; p = 0.04). The three most frequent PyVs were MCPyV, HPyV6 and JCPyV (HS: 87.2%, 58.7%, 6.6%, respectively; AK: 88.8%, 51.2%, 9.9%, respectively). HPyV9, TSPyV, BKPyV, HPyV7, LIPyV and SV40 were detected in < 2% of the scrapings. In most cases, matched HS and AK scrapings were both positive (MCPyV: 78.1%, HPyV6: 41.7%), or both negative for the individual genotypes (for the remaining PyVs). PyV prevalence in AK biopsies was 22.0%. Only MCPyV (21.0%) and HPyV6 (3.0%) were detected in these samples. Conclusions: PyV prevalence in HS and AK scrapings was high, but detection of PyVs exclusively in AK scrapings was rare. PyV positivity rate in AK biopsies was modest. Further research is need to reach firm conclusions regarding the role of these viruses in AK development.
Language	English
Publishing date	2022-12-01
Publishing country	England
Document type	Journal Article
ZDB-ID	2251117-9
ISSN	1750-9378
ISSN	1750-9378
DOI	10.1186/s13027-022-00472-w
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Article: Epigenetic Alteration of the Cancer-Related Gene TGFBI in B Cells Infected with Epstein-Barr Virus and Exposed to Aflatoxin B1: Potential Role in Burkitt Lymphoma Development.

Manara, Francesca / Jay, Antonin / Odongo, Grace Akinyi / Mure, Fabrice / Maroui, Mohamed Ali / Diederichs, Audrey / Sirand, Cecilia / Cuenin, Cyrille / Granai, Massimo / Mundo, Lucia / Hernandez-Vargas, Hector / Lazzi, Stefano / Khoueiry, Rita / Gruffat, Henri / Herceg, Zdenko / Accardi, Rosita

Cancers

2022 Volume 14, Issue 5

Abstract: Burkitt lymphoma (BL) is a malignant B cell neoplasm that accounts for almost half of pediatric cancers in sub-Saharan African countries. Although the BL endemic prevalence is attributable to the combination of Epstein-Barr virus (EBV) infection with ... ...

Abstract	Burkitt lymphoma (BL) is a malignant B cell neoplasm that accounts for almost half of pediatric cancers in sub-Saharan African countries. Although the BL endemic prevalence is attributable to the combination of Epstein-Barr virus (EBV) infection with malaria and environmental carcinogens exposure, such as the food contaminant aflatoxin B1 (AFB1), the molecular determinants underlying the pathogenesis are not fully understood. Consistent with the role of epigenetic mechanisms at the interface between the genome and environment, AFB1 and EBV impact the methylome of respectively leukocytes and B cells specifically. Here, we conducted a thorough investigation of common epigenomic changes following EBV or AFB1 exposure in B cells. Genome-wide DNA methylation profiling identified an EBV-AFB1 common signature within the TGFBI locus, which encodes for a putative tumor suppressor often altered in cancer. Subsequent mechanistic analyses confirmed a DNA-methylation-dependent transcriptional silencing of TGFBI involving the recruitment of DNMT1 methyltransferase that is associated with an activation of the NF-κB pathway. Our results reveal a potential common mechanism of B cell transformation shared by the main risk factors of endemic BL (EBV and AFB1), suggesting a key determinant of disease that could allow the development of more efficient targeted therapeutic strategies.
Language	English
Publishing date	2022-03-02
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers14051284
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Article ; Online: The Role of Matrix Metalloproteinases (MMP-2 and MMP-9) in Ageing and Longevity: Focus on Sicilian Long-Living Individuals (LLIs).

Cancemi, Patrizia / Aiello, Anna / Accardi, Giulia / Caldarella, Rosalia / Candore, Giuseppina / Caruso, Calogero / Ciaccio, Marcello / Cristaldi, Laura / Di Gaudio, Francesca / Siino, Valentina / Vasto, Sonya

Mediators of inflammation

2020 Volume 2020, Page(s) 8635158

Abstract: Extracellular matrix metalloproteinases (MMPs) are a group of proteins that activate substrates by enzymatic cleavage and, on the basis of their activities, have been demonstrated to play a role in ageing. Thus, in order to gain insight into the ... ...

Abstract	Extracellular matrix metalloproteinases (MMPs) are a group of proteins that activate substrates by enzymatic cleavage and, on the basis of their activities, have been demonstrated to play a role in ageing. Thus, in order to gain insight into the pathophysiology of ageing and to identify new markers of longevity, we analysed the activity levels of MMP-2 and MMP-9 in association with some relevant haematochemical parameters in a Sicilian population, including long-living individuals (LLIs, ≥95 years old). A cohort of 154 healthy subjects (72 men and 82 women) of different ages (age range 20-112) was recruited. The cohort was divided into five subgroups: the first group with subjects less than 40 years old, the second group ranging from 40 to 64 years old, the third group ranging from 65 to 89 years old, the fourth group ranging from 90 to 94 years old, and the fifth group with subjects more than 95 years old. A relationship was observed between LLIs and MMP-2, but not between LLIs and MMP-9. However, in the LLI group, MMP-2 and MMP-9 values were significantly correlated. Furthermore, in LLIs, we found a positive correlation of MMP-2 with the antioxidant catabolite uric acid and a negative correlation with the inflammatory marker C-reactive protein. Finally, in LLIs MMP-9 values correlated directly both with cholesterol and with low-density lipoproteins. On the whole, our data suggest that the observed increase of MMP-2 in LLIs might play a positive role in the attainment of longevity. This is the first study that shows that serum activity of MMP-2 is increased in LLIs as compared to younger subjects. As far as we are concerned, it is difficult to make wide-ranging conclusions/assumptions based on these observations in view of the relatively small sample size of LLIs. However, this is an important starting point. Larger-scale future studies will be required to clarify these findings including the link with other systemic inflammatory and antioxidant markers.
Language	English
Publishing date	2020-05-05
Publishing country	United States
Document type	Journal Article
ZDB-ID	1137605-3
ISSN	1466-1861 ; 0962-9351
ISSN (online)	1466-1861
ISSN	0962-9351
DOI	10.1155/2020/8635158
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Article ; Online: A novel intracellular antibody against the E6 oncoprotein impairs growth of human papillomavirus 16-positive tumor cells in mouse models.

Amici, Carla / Visintin, Michela / Verachi, Francesca / Paolini, Francesca / Percario, Zulema / Di Bonito, Paola / Mandarino, Angela / Affabris, Elisabetta / Venuti, Aldo / Accardi, Luisa

Oncotarget

2016 Volume 7, Issue 13, Page(s) 15539–15553

Abstract: Single-chain variable fragments (scFvs) expressed as "intracellular antibodies" (intrabodies) can target intracellular antigens to hamper their function efficaciously and specifically. Here we use an intrabody targeting the E6 oncoprotein of Human ... ...

Abstract	Single-chain variable fragments (scFvs) expressed as "intracellular antibodies" (intrabodies) can target intracellular antigens to hamper their function efficaciously and specifically. Here we use an intrabody targeting the E6 oncoprotein of Human papillomavirus 16 (HPV16) to address the issue of a non-invasive therapy for HPV cancer patients.A scFv against the HPV16 E6 was selected by Intracellular Antibody Capture Technology and expressed as I7nuc in the nucleus of HPV16-positive SiHa, HPV-negative C33A and 293T cells. Colocalization of I7nuc and recombinant E6 was observed in different cell compartments, obtaining evidence of E6 delocalization ascribable to I7nuc. In SiHa cells, I7nuc expressed by pLNCX retroviral vector was able to partially inhibit degradation of the main E6 target p53, and induced p53 accumulation in nucleus. When analyzing in vitro activity on cell proliferation and survival, I7nuc was able to decrease growth inducing late apoptosis and necrosis of SiHa cells.Finally, I7nuc antitumor activity was demonstrated in two pre-clinical models of HPV tumors. C57BL/6 mice were injected subcutaneously with HPV16-positive TC-1 or C3 tumor cells, infected with pLNCX retroviral vector expressing or non-expressing I7nuc. All the mice injected with I7nuc-expressing cells showed a clear delay in tumor onset; 60% and 40% of mice receiving TC-1 and C3 cells, respectively, remained tumor-free for 17 weeks of follow-up, whereas 100% of the controls were tumor-bearing 20 days post-inoculum. Our data support the therapeutic potential of E6-targeted I7nuc against HPV tumors.
Language	English
Publishing date	2016-03-29
Publishing country	United States
Document type	Journal Article
ZDB-ID	2560162-3
ISSN	1949-2553 ; 1949-2553
ISSN (online)	1949-2553
ISSN	1949-2553
DOI	10.18632/oncotarget.6925
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Article ; Online: Dietary Supplements as Surrogate of Mediterranean Diet in Healthy Smoking Subjects.

Vasto, Sonya / Accardi, Giulia / Aiello, Anna / Di Gaudio, Francesca / Barera, Annalisa / Indelicato, Serena / Galimberti, Damiano / Italiano, Emilio / Monastero, Roberto / Rizzo, Claudia / Caruso, Calogero / Candore, Giuseppina

Rejuvenation research

2017 Volume 21, Issue 1, Page(s) 37–43

Abstract: The interventions to slow aging, favoring active life expectancy, represent the new perspectives in ageing investigation. Some mechanisms that delay or prevent the onset of aging pathologies have been identified. Between them, a healthy lifestyle seems ... ...

Abstract	The interventions to slow aging, favoring active life expectancy, represent the new perspectives in ageing investigation. Some mechanisms that delay or prevent the onset of aging pathologies have been identified. Between them, a healthy lifestyle seems to reduce many risk factors. In particular, eating habits represent the most concrete, low-cost way to act on aging process. Mediterranean diet has received much attention since its antioxidant and anti-inflammatory effects have been consistently demonstrated. Unfortunately, many people follow a Western diet, poor in phytochemicals that represent the main source of beneficial effects of this dietary pattern. So, supplements administration should be considered, especially in subjects exposed to high level of oxidative stress and inflammation. So, we tested the properties of a commercial food supplement containing a series of plant polyphenols in combination with caffeine, bioperine (black pepper extract), and selenium in smoking healthy volunteers. Fifty participants have been recruited and hematochemical analyses and biochemistry tests have been performed, before and after 60 days of supplement intake. Thirteen subjects dropped out of the study. At the end of the intervention, the variation of inflammatory and oxidant markers has been evaluated, measuring urinary isoprostanes, serum advanced glycation end products, and oxidized low-density lipoproteins. The results showed that this supplement exhibits promising antioxidant and anti-inflammatory responses, especially in women, highlighting the role of supplementation in certain groups of subjects, for the control of oxidative stress as well as inflammatory status. So, its intake should be useful in delaying the onset of age-related diseases.
MeSH term(s)	Anthropometry ; Diet, Mediterranean ; Dietary Supplements ; Female ; Glycation End Products, Advanced/metabolism ; Health ; Humans ; Isoprostanes/metabolism ; Lipoproteins, LDL/metabolism ; Male ; Middle Aged ; Smoking
Chemical Substances	Glycation End Products, Advanced ; Isoprostanes ; Lipoproteins, LDL ; oxidized low density lipoprotein
Language	English
Publishing date	2017-06-26
Publishing country	United States
Document type	Journal Article
ZDB-ID	2150779-X
ISSN	1557-8577 ; 1549-1684
ISSN (online)	1557-8577
ISSN	1549-1684
DOI	10.1089/rej.2017.1950
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Article ; Online: Interplay between the Epigenetic Enzyme Lysine (K)-Specific Demethylase 2B and Epstein-Barr Virus Infection.

Journal of virology

2019 Volume 93, Issue 13

Abstract: The histone modifier lysine (K)-specific demethylase 2B (KDM2B) plays a role in the differentiation of hematopoietic cells, and its expression appears to be deregulated in certain cancers of hematological and lymphoid origins. We have previously found ... ...

Abstract	The histone modifier lysine (K)-specific demethylase 2B (KDM2B) plays a role in the differentiation of hematopoietic cells, and its expression appears to be deregulated in certain cancers of hematological and lymphoid origins. We have previously found that the
MeSH term(s)	Adolescent ; Adult ; B-Lymphocytes/virology ; Burkitt Lymphoma/metabolism ; Cell Line ; Child ; Child, Preschool ; Chromatin/metabolism ; Chromatin Immunoprecipitation ; DNA Methylation ; Down-Regulation ; Epigenesis, Genetic ; Epstein-Barr Virus Infections/genetics ; Epstein-Barr Virus Infections/metabolism ; F-Box Proteins/genetics ; F-Box Proteins/metabolism ; Female ; Gene Expression Regulation ; Herpesvirus 4, Human/physiology ; Humans ; Jumonji Domain-Containing Histone Demethylases/genetics ; Jumonji Domain-Containing Histone Demethylases/metabolism ; Male ; Middle Aged ; Young Adult
Chemical Substances	Chromatin ; F-Box Proteins ; Jumonji Domain-Containing Histone Demethylases (EC 1.14.11.-) ; KDM2A protein, human (EC 1.14.11.27)
Language	English
Publishing date	2019-06-14
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80174-4
ISSN	1098-5514 ; 0022-538X
ISSN (online)	1098-5514
ISSN	0022-538X
DOI	10.1128/JVI.00273-19
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