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Article ; Online: Infection by High-Risk Human Papillomaviruses, Epithelial-to-Mesenchymal Transition and Squamous Pre-Malignant or Malignant Lesions of the Uterine Cervix: A Series of Chained Events?

Barillari, Giovanni / Bei, Roberto / Manzari, Vittorio / Modesti, Andrea

International journal of molecular sciences

2021 Volume 22, Issue 24

Abstract: Wound healing requires static epithelial cells to gradually assume a mobile phenotype through a multi-step process termed epithelial-to-mesenchymal transition (EMT). Although it is inherently transient and reversible, EMT perdures and is abnormally ... ...

Abstract	Wound healing requires static epithelial cells to gradually assume a mobile phenotype through a multi-step process termed epithelial-to-mesenchymal transition (EMT). Although it is inherently transient and reversible, EMT perdures and is abnormally activated when the epithelium is chronically exposed to pathogens: this event deeply alters the tissue and eventually contributes to the development of diseases. Among the many of them is uterine cervical squamous cell carcinoma (SCC), the most frequent malignancy of the female genital system. SCC, whose onset is associated with the persistent infection of the uterine cervix by high-risk human papillomaviruses (HR-HPVs), often relapses and/or metastasizes, being resistant to conventional chemo- or radiotherapy. Given that these fearsome clinical features may stem, at least in part, from the exacerbated and long-lasting EMT occurring in the HPV-infected cervix; here we have reviewed published studies concerning the impact that HPV oncoproteins, cellular tumor suppressors, regulators of gene expression, inflammatory cytokines or growth factors, and the interactions among these effectors have on EMT induction and cervical carcinogenesis. It is predictable and desirable that a broader comprehension of the role that EMT inducers play in SCC pathogenesis will provide indications to flourish new strategies directed against this aggressive tumor.
MeSH term(s)	Alphapapillomavirus ; Carcinoma, Squamous Cell/etiology ; Carcinoma, Squamous Cell/physiopathology ; Epithelial-Mesenchymal Transition ; Female ; Humans ; Inflammation ; Papillomavirus Infections/complications ; Uterine Cervical Neoplasms/etiology ; Uterine Cervical Neoplasms/physiopathology
Language	English
Publishing date	2021-12-17
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms222413543
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: SARS-COV-2 and infectivity: Possible increase in infectivity associated to integrin motif expression.

Tresoldi, Ilaria / Sangiuolo, Carla F / Manzari, Vittorio / Modesti, Andrea

Journal of medical virology

2020 Volume 92, Issue 10, Page(s) 1741–1742

MeSH term(s)	COVID-19/virology ; Humans ; Integrins/genetics ; Pandemics ; SARS-CoV-2/genetics ; SARS-CoV-2/pathogenicity ; Spike Glycoprotein, Coronavirus/genetics
Chemical Substances	Integrins ; Spike Glycoprotein, Coronavirus
Keywords	covid19
Language	English
Publishing date	2020-04-10
Publishing country	United States
Document type	Letter
ZDB-ID	752392-0
ISSN	1096-9071 ; 0146-6615
ISSN (online)	1096-9071
ISSN	0146-6615
DOI	10.1002/jmv.25831
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Article ; Online: 3D Printing Decellularized Extracellular Matrix to Design Biomimetic Scaffolds for Skeletal Muscle Tissue Engineering.

Baiguera, Silvia / Del Gaudio, Costantino / Di Nardo, Paolo / Manzari, Vittorio / Carotenuto, Felicia / Teodori, Laura

BioMed research international

2020 Volume 2020, Page(s) 2689701

Abstract: Functional engineered muscles are still a critical clinical issue to be addressed, although different strategies have been considered so far for the treatment of severe muscular injuries. Indeed, the regenerative capacity of skeletal muscle (SM) results ... ...

Abstract	Functional engineered muscles are still a critical clinical issue to be addressed, although different strategies have been considered so far for the treatment of severe muscular injuries. Indeed, the regenerative capacity of skeletal muscle (SM) results inadequate for large-scale defects, and currently, SM reconstruction remains a complex and unsolved task. For this aim, tissue engineered muscles should provide a proper biomimetic extracellular matrix (ECM) alternative, characterized by an aligned/microtopographical structure and a myogenic microenvironment, in order to promote muscle regeneration. As a consequence, both materials and fabrication techniques play a key role to plan an effective therapeutic approach. Tissue-specific decellularized ECM (dECM) seems to be one of the most promising material to support muscle regeneration and repair. 3D printing technologies, on the other side, enable the fabrication of scaffolds with a fine and detailed microarchitecture and patient-specific implants with high structural complexity. To identify innovative biomimetic solutions to develop engineered muscular constructs for the treatment of SM loss, the more recent (last 5 years) reports focused on SM dECM-based scaffolds and 3D printing technologies for SM regeneration are herein reviewed. Possible design inputs for 3D printed SM dECM-based scaffolds for muscular regeneration are also suggested.
MeSH term(s)	Animals ; Biomimetic Materials/chemistry ; Extracellular Matrix/metabolism ; Humans ; Muscle, Skeletal/physiology ; Printing, Three-Dimensional ; Tissue Engineering ; Tissue Scaffolds/chemistry
Language	English
Publishing date	2020-11-17
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2698540-8
ISSN	2314-6141 ; 2314-6133
ISSN (online)	2314-6141
ISSN	2314-6133
DOI	10.1155/2020/2689701
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Article: SARS-COV-2 and infectivity: Possible increase in infectivity associated to integrin motif expression

Tresoldi, Ilaria / Sangiuolo, Carla F / Manzari, Vittorio / Modesti, Andrea

J. med. virol

Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #87350
Database	COVID19

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Article ; Online: Multifaceted Role of the Placental Growth Factor (PlGF) in the Antitumor Immune Response and Cancer Progression.

Albonici, Loredana / Giganti, Maria Gabriella / Modesti, Andrea / Manzari, Vittorio / Bei, Roberto

International journal of molecular sciences

2019 Volume 20, Issue 12

Abstract: The sharing of molecules function that affects both tumor growth and neoangiogenesis with cells of the immune system creates a mutual interplay that impairs the host's immune response against tumor progression. Increasing evidence shows that tumors are ... ...

Abstract	The sharing of molecules function that affects both tumor growth and neoangiogenesis with cells of the immune system creates a mutual interplay that impairs the host's immune response against tumor progression. Increasing evidence shows that tumors are able to create an immunosuppressive microenvironment by recruiting specific immune cells. Moreover, molecules produced by tumor and inflammatory cells in the tumor microenvironment create an immunosuppressive milieu able to inhibit the development of an efficient immune response against cancer cells and thus fostering tumor growth and progression. In addition, the immunoediting could select cancer cells that are less immunogenic or more resistant to lysis. In this review, we summarize recent findings regarding the immunomodulatory effects and cancer progression of the angiogenic growth factor namely placental growth factor (PlGF) and address the biological complex effects of this cytokine. Different pathways of the innate and adaptive immune response in which, directly or indirectly, PlGF is involved in promoting tumor immune escape and metastasis will be described. PlGF is important for building up vascular structures and functions. Although PlGF effects on vascular and tumor growth have been widely summarized, its functions in modulating the immune intra-tumoral microenvironment have been less highlighted. In agreement with PlGF functions, different antitumor strategies can be envisioned.
MeSH term(s)	Angiogenesis Inducing Agents/metabolism ; Animals ; Disease Progression ; Drug Evaluation, Preclinical ; Humans ; Immunologic Surveillance ; Immunomodulation ; Molecular Targeted Therapy ; Neoplasms/drug therapy ; Neoplasms/etiology ; Neoplasms/metabolism ; Neoplasms/pathology ; Neovascularization, Pathologic/genetics ; Neovascularization, Pathologic/immunology ; Neovascularization, Pathologic/metabolism ; Placenta Growth Factor/genetics ; Placenta Growth Factor/metabolism ; Receptors, Neuropeptide/metabolism ; Signal Transduction
Chemical Substances	Angiogenesis Inducing Agents ; Receptors, Neuropeptide ; Placenta Growth Factor (144589-93-5)
Language	English
Publishing date	2019-06-18
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms20122970
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Article: The ETS Homologous Factor (EHF) Represents a Useful Immunohistochemical Marker for Predicting Prostate Cancer Metastasis.

Scimeca, Manuel / Montanaro, Manuela / Bonfiglio, Rita / Anemona, Lucia / Agrò, Enrico Finazzi / Asimakopoulos, Anastasios D / Bei, Roberto / Manzari, Vittorio / Urbano, Nicoletta / Giacobbi, Erica / Servadei, Francesca / Bonanno, Elena / Schillaci, Orazio / Mauriello, Alessandro

Diagnostics (Basel, Switzerland)

2022 Volume 12, Issue 4

Abstract: The main aim of this study was to investigate the risk of prostate cancer metastasis formation associated with the expression of ETS homologous factor (EHF) in a cohort of bioptic samples. To this end, the expression of EHF was evaluated in a cohort of ... ...

Abstract	The main aim of this study was to investigate the risk of prostate cancer metastasis formation associated with the expression of ETS homologous factor (EHF) in a cohort of bioptic samples. To this end, the expression of EHF was evaluated in a cohort of 152 prostate biopsies including primary prostate cancers that developed metastatic lesions, primary prostate cancers that did not develop metastasis, and benign lesions. Data here reported EHF as a candidate immunohistochemical prognostic biomarker for prostate cancer metastasis formation regardless of the Gleason scoring system. Indeed, our data clearly show that primary lesions with EHF positive cells ≥40% had a great risk of developing metastasis within five years from the first diagnosis. Patients with these lesions had about a 40-fold increased risk of developing metastasis as compared with patients with prostate lesions characterized by a percentage of EHF positive cells ≤30%. In conclusion, the immunohistochemical evaluation of EHF could significantly improve the management of prostate cancer patients by optimizing the diagnostic and therapeutic health procedures and, more important, ameliorating the patient's quality of life.
Language	English
Publishing date	2022-03-24
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662336-5
ISSN	2075-4418
ISSN	2075-4418
DOI	10.3390/diagnostics12040800
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Article ; Online: Interoperability Among Unmanned Maritime Vehicles: Review and First In-field Experimentation.

Costanzi, Riccardo / Fenucci, Davide / Manzari, Vincenzo / Micheli, Michele / Morlando, Luca / Terracciano, Daniele / Caiti, Andrea / Stifani, Mirko / Tesei, Alessandra

Frontiers in robotics and AI

2020 Volume 7, Page(s) 91

Abstract: Complex maritime missions, both above and below the surface, have traditionally been carried out by manned surface ships and submarines equipped with advanced sensor systems. Unmanned Maritime Vehicles (UMVs) are increasingly demonstrating their ... ...

Abstract	Complex maritime missions, both above and below the surface, have traditionally been carried out by manned surface ships and submarines equipped with advanced sensor systems. Unmanned Maritime Vehicles (UMVs) are increasingly demonstrating their potential for improving existing naval capabilities due to their rapid deployability, easy scalability, and high reconfigurability, offering a reduction in both operational time and cost. In addition, they mitigate the risk to personnel by leaving the man far-from-the-risk but in-the-loop of decision making. In the long-term, a clear interoperability framework between unmanned systems, human operators, and legacy platforms will be crucial for effective joint operations planning and execution. However, the present multi-vendor multi-protocol solutions in multi-domain UMVs activities are hard to interoperate without common mission control interfaces and communication protocol schemes. Furthermore, the underwater domain presents significant challenges that cannot be satisfied with the solutions developed for terrestrial networks. In this paper, the interoperability topic is discussed blending a review of the technological growth from 2000 onwards with recent authors' in-field experience; finally, important research directions for the future are given. Within the broad framework of interoperability in general, the paper focuses on the aspect of interoperability among UMVs not neglecting the role of the human operator in the loop. The picture emerging from the review demonstrates that interoperability is currently receiving a high level of attention with a great and diverse deal of effort. Besides, the manuscript describes the experience from a sea trial exercise, where interoperability has been demonstrated by integrating heterogeneous autonomous UMVs into the NATO Centre for Maritime Research and Experimentation (CMRE) network, using different robotic middlewares and acoustic modem technologies to implement a multistatic active sonar system. A perspective for the interoperability in marine robotics missions emerges in the paper, through a discussion of current capabilities, in-field experience and future advanced technologies unique to UMVs. Nonetheless, their application spread is slowed down by the lack of human confidence. In fact, an interoperable system-of-systems of autonomous UMVs will require operators involved only at a supervisory level. As trust develops, endorsed by stable and mature interoperability, human monitoring will be diminished to exploit the tremendous potential of fully autonomous UMVs.
Language	English
Publishing date	2020-07-14
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2781824-X
ISSN	2296-9144 ; 2296-9144
ISSN (online)	2296-9144
ISSN	2296-9144
DOI	10.3389/frobt.2020.00091
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Article ; Online: PlGF Immunological Impact during Pregnancy.

Albonici, Loredana / Benvenuto, Monica / Focaccetti, Chiara / Cifaldi, Loredana / Miele, Martino Tony / Limana, Federica / Manzari, Vittorio / Bei, Roberto

International journal of molecular sciences

2020 Volume 21, Issue 22

Abstract: During pregnancy, the mother's immune system has to tolerate the persistence of paternal alloantigens without affecting the anti-infectious immune response. Consequently, several mechanisms aimed at preventing allograft rejection, occur during a ... ...

Abstract	During pregnancy, the mother's immune system has to tolerate the persistence of paternal alloantigens without affecting the anti-infectious immune response. Consequently, several mechanisms aimed at preventing allograft rejection, occur during a pregnancy. In fact, the early stages of pregnancy are characterized by the correct balance between inflammation and immune tolerance, in which proinflammatory cytokines contribute to both the remodeling of tissues and to neo-angiogenesis, thus, favoring the correct embryo implantation. In addition to the creation of a microenvironment able to support both immunological privilege and angiogenesis, the trophoblast invades normal tissues by sharing the same behavior of invasive tumors. Next, the activation of an immunosuppressive phase, characterized by an increase in the number of regulatory T (Treg) cells prevents excessive inflammation and avoids fetal immuno-mediated rejection. When these changes do not occur or occur incompletely, early pregnancy failure follows. All these events are characterized by an increase in different growth factors and cytokines, among which one of the most important is the angiogenic growth factor, namely placental growth factor (PlGF). PlGF is initially isolated from the human placenta. It is upregulated during both pregnancy and inflammation. In this review, we summarize current knowledge on the immunomodulatory effects of PlGF during pregnancy, warranting that both innate and adaptive immune cells properly support the early events of implantation and placental development. Furthermore, we highlight how an alteration of the immune response, associated with PlGF imbalance, can induce a hypertensive state and lead to the pre-eclampsia (PE).
MeSH term(s)	Adaptive Immunity/immunology ; Cytokines/immunology ; Cytokines/metabolism ; Female ; Humans ; Immunity, Innate/immunology ; Inflammation Mediators/immunology ; Inflammation Mediators/metabolism ; Placenta/immunology ; Placenta/metabolism ; Placenta Growth Factor/immunology ; Placenta Growth Factor/metabolism ; Pre-Eclampsia/immunology ; Pre-Eclampsia/metabolism ; Pregnancy
Chemical Substances	Cytokines ; Inflammation Mediators ; Placenta Growth Factor (144589-93-5)
Language	English
Publishing date	2020-11-18
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms21228714
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Article: Smart ECM-Based Electrospun Biomaterials for Skeletal Muscle Regeneration.

Politi, Sara / Carotenuto, Felicia / Rinaldi, Antonio / Di Nardo, Paolo / Manzari, Vittorio / Albertini, Maria Cristina / Araneo, Rodolfo / Ramakrishna, Seeram / Teodori, Laura

Nanomaterials (Basel, Switzerland)

2020 Volume 10, Issue 9

Abstract: The development of smart and intelligent regenerative biomaterials for skeletal muscle tissue engineering is an ongoing challenge, owing to the requirement of achieving biomimetic systems able to communicate biological signals and thus promote optimal ... ...

Abstract	The development of smart and intelligent regenerative biomaterials for skeletal muscle tissue engineering is an ongoing challenge, owing to the requirement of achieving biomimetic systems able to communicate biological signals and thus promote optimal tissue regeneration. Electrospinning is a well-known technique to produce fibers that mimic the three dimensional microstructural arrangements, down to nanoscale and the properties of the extracellular matrix fibers. Natural and synthetic polymers are used in the electrospinning process; moreover, a blend of them provides composite materials that have demonstrated the potential advantage of supporting cell function and adhesion. Recently, the decellularized extracellular matrix (dECM), which is the noncellular component of tissue that retains relevant biological cues for cells, has been evaluated as a starting biomaterial to realize composite electrospun constructs. The properties of the electrospun systems can be further improved with innovative procedures of functionalization with biomolecules. Among the various approaches, great attention is devoted to the "click" concept in constructing a bioactive system, due to the modularity, orthogonality, and simplicity features of the "click" reactions. In this paper, we first provide an overview of current approaches that can be used to obtain biofunctional composite electrospun biomaterials. Finally, we propose a design of composite electrospun biomaterials suitable for skeletal muscle tissue regeneration.
Language	English
Publishing date	2020-09-09
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2662255-5
ISSN	2079-4991
ISSN	2079-4991
DOI	10.3390/nano10091781
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Article ; Online: Combined treatment with inhibitors of ErbB Receptors and Hh signaling pathways is more effective than single treatment in reducing the growth of malignant mesothelioma both in vitro and in vivo.

Bei, Roberto / Benvenuto, Monica / Focaccetti, Chiara / Fazi, Sara / Moretti, Marta / Nardozi, Daniela / Angiolini, Valentina / Ciuffa, Sara / Cifaldi, Loredana / Carrano, Raffaele / Palumbo, Camilla / Miele, Martino Tony / Bei, Riccardo / Barillari, Giovanni / Manzari, Vittorio / De Smaele, Enrico / Modesti, Andrea / Masuelli, Laura

Journal of translational medicine

2022 Volume 20, Issue 1, Page(s) 286

Abstract: Malignant mesothelioma (MM) is a rare orphan aggressive neoplasia with low survival rates. Among the other signaling pathways, ErbB receptors and Hh signaling are deregulated in MM. Thus, molecules involved in these signaling pathways could be used for ... ...

Abstract	Malignant mesothelioma (MM) is a rare orphan aggressive neoplasia with low survival rates. Among the other signaling pathways, ErbB receptors and Hh signaling are deregulated in MM. Thus, molecules involved in these signaling pathways could be used for targeted therapy approaches. The aim of this study was to evaluate the effects of inhibitors of Hh- (GANT-61) and ErbB receptors (Afatinib)-mediated signaling pathways, when used alone or in combination, on growth, cell cycle, cell death and autophagy, modulation of molecules involved in transduction pathways, in three human MM cell lines of different histotypes. The efficacy of the combined treatment was also evaluated in a murine epithelioid MM cell line both in vitro and in vivo. This study demonstrated that combined treatment with two inhibitors counteracting the activation of two different signaling pathways involved in neoplastic transformation and progression, such as those activated by ErbB and Hh signaling, is more effective than the single treatments in reducing MM growth in vitro and in vivo. This study may have clinical implications for the development of targeted therapy approaches for MM.
MeSH term(s)	Animals ; Cell Line, Tumor ; ErbB Receptors/metabolism ; Hedgehog Proteins ; Humans ; Mesothelioma, Malignant ; Mice ; Signal Transduction ; Zinc Finger Protein GLI1
Chemical Substances	Hedgehog Proteins ; Zinc Finger Protein GLI1 ; ErbB Receptors (EC 2.7.10.1)
Language	English
Publishing date	2022-06-25
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2118570-0
ISSN	1479-5876 ; 1479-5876
ISSN (online)	1479-5876
ISSN	1479-5876
DOI	10.1186/s12967-022-03490-9
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