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  1. Article ; Online: Canine glioblastoma-derived extracellular vesicles as precise carriers for glioblastoma imaging: Targeting across the blood-brain barrier.

    Villa, Alessandro / De Mitri, Zemira / Vincenti, Simona / Crippa, Elisabetta / Castiglioni, Laura / Gelosa, Paolo / Rebecchi, Monica / Tosi, Delfina / Brunialti, Electra / Oevermann, Anna / Falleni, Monica / Sironi, Luigi / Bello, Lorenzo / Mazzaferro, Vincenzo / Ciana, Paolo

    Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie

    2024  Volume 172, Page(s) 116201

    Abstract: The treatment of glioblastoma (GBM) faces significant challenges due to the difficulty of delivering drugs through the blood-brain barrier (BBB). Extracellular vesicles (EVs) have emerged as potential carriers for targeted drug delivery to brain tumors. ... ...

    Abstract The treatment of glioblastoma (GBM) faces significant challenges due to the difficulty of delivering drugs through the blood-brain barrier (BBB). Extracellular vesicles (EVs) have emerged as potential carriers for targeted drug delivery to brain tumors. However, their use and distribution in the presence of an intact BBB and their ability to target GBM tissue are still under investigation. This study explored the use of EVs for GBM targeting across the BBB. Canine plasma EVs from healthy dogs and dogs with glioma were isolated, characterized, and loaded with diagnostic agents. Biodistribution studies were conducted in healthy murine models and a novel intranasal model that preserved BBB integrity while initiating early-stage GBM growth. This model assessed EVs' potential for delivering the contrast agent gadoteric acid to intracranial tumors. Imaging techniques, such as bioluminescence and MRI, confirmed EVs' targeting and delivery capabilities thus revealing a selective accumulation of canine glioma-derived EVs in brain tissue under physiological conditions. In the model of brain tumor, MRI experiments demonstrated the ability of EVs to accumulate gadoteric acid within GBM to enhance contrast of the tumoral mass, even when BBB integrity is maintained. This study underscores the potential of EVs derived from glioma for the targeted delivery of drugs to glioblastoma. EVs from dogs with glioma showed capacity to traverse the BBB and selectively accumulate within the brain tumor. Overall, this research represents a foundation for the application of autologous EVs to precision glioblastoma treatment, addressing the challenge of BBB penetration and targeting specificity in brain cancer therapy.
    MeSH term(s) Dogs ; Animals ; Mice ; Glioblastoma/diagnostic imaging ; Blood-Brain Barrier ; Tissue Distribution ; Glioma ; Brain Neoplasms/diagnostic imaging ; Chelating Agents ; Contrast Media ; Extracellular Vesicles
    Chemical Substances Chelating Agents ; Contrast Media
    Language English
    Publishing date 2024-02-01
    Publishing country France
    Document type Journal Article
    ZDB-ID 392415-4
    ISSN 1950-6007 ; 0753-3322 ; 0300-0893
    ISSN (online) 1950-6007
    ISSN 0753-3322 ; 0300-0893
    DOI 10.1016/j.biopha.2024.116201
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Endothelial-Mesenchymal Transition in COVID-19 lung lesions.

    Falleni, Monica / Tosi, Delfina / Savi, Federica / Chiumello, Davide / Bulfamante, Gaetano

    Pathology, research and practice

    2021  Volume 221, Page(s) 153419

    Abstract: Sars-Cov-2 infection is still a healthcare emergency and acute respiratory distress failure with Diffuse Alveolar Damage (DAD) features is the main causes of patients' death. Pathogenic mechanisms of the disease are not clear yet, but new insights are ... ...

    Abstract Sars-Cov-2 infection is still a healthcare emergency and acute respiratory distress failure with Diffuse Alveolar Damage (DAD) features is the main causes of patients' death. Pathogenic mechanisms of the disease are not clear yet, but new insights are necessary to improve therapeutic management, to prevent fatal irreversible multi-organ damage and to adequately follow up those patients who survive. Here we investigated, by histochemistry and immunohistochemistry, a wide number of mapped lung specimens taken from whole body autopsies of 7 patients dead of COVID-19 disease. Our data confirm morphological data of other authors, and enlarge recent reports of the literature suggesting that Endothelial-Mesenchymal Transition might be central to COVID-19 lung fibrosing lesions. Furthermore, based upon recent acquisition of new roles in immunity and vascular pathology of the CD31 molecule, we hypothesize that this molecule might be important in the development and treatment of COVID-19 pulmonary lesions. These preliminary findings need further investigations to shed light on the complexity of Sars-Cov-2 disease.
    MeSH term(s) Aged ; COVID-19/pathology ; Epithelial-Mesenchymal Transition ; Female ; Humans ; Lung Diseases/pathology ; Lung Diseases/virology ; Male ; Middle Aged ; SARS-CoV-2
    Language English
    Publishing date 2021-03-26
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 391889-0
    ISSN 1618-0631 ; 0344-0338
    ISSN (online) 1618-0631
    ISSN 0344-0338
    DOI 10.1016/j.prp.2021.153419
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Brainstem clinical and neurophysiological involvement in COVID-19.

    Bocci, Tommaso / Bulfamante, Gaetano / Campiglio, Laura / Coppola, Silvia / Falleni, Monica / Chiumello, Davide / Priori, Alberto

    Journal of neurology

    2021  Volume 268, Issue 10, Page(s) 3598–3600

    MeSH term(s) Brain Stem/diagnostic imaging ; COVID-19 ; Humans ; Neurophysiology ; SARS-CoV-2
    Language English
    Publishing date 2021-03-18
    Publishing country Germany
    Document type Letter
    ZDB-ID 187050-6
    ISSN 1432-1459 ; 0340-5354 ; 0012-1037 ; 0939-1517 ; 1619-800X
    ISSN (online) 1432-1459
    ISSN 0340-5354 ; 0012-1037 ; 0939-1517 ; 1619-800X
    DOI 10.1007/s00415-021-10474-0
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: The Potential of JAG Ligands as Therapeutic Targets and Predictive Biomarkers in Multiple Myeloma.

    Platonova, Natalia / Lazzari, Elisa / Colombo, Michela / Falleni, Monica / Tosi, Delfina / Giannandrea, Domenica / Citro, Valentina / Casati, Lavinia / Ronchetti, Domenica / Bolli, Niccolò / Neri, Antonino / Torricelli, Federica / Crews, Leslie A / Jamieson, Catriona H M / Chiaramonte, Raffaella

    International journal of molecular sciences

    2023  Volume 24, Issue 19

    Abstract: The NOTCH ligands JAG1 and JAG2 have been correlated in vitro with multiple myeloma (MM) cell proliferation, drug resistance, self-renewal and a pathological crosstalk with the tumor microenvironment resulting in angiogenesis and osteoclastogenesis. ... ...

    Abstract The NOTCH ligands JAG1 and JAG2 have been correlated in vitro with multiple myeloma (MM) cell proliferation, drug resistance, self-renewal and a pathological crosstalk with the tumor microenvironment resulting in angiogenesis and osteoclastogenesis. These findings suggest that a therapeutic approach targeting JAG ligands might be helpful for the care of MM patients and lead us to explore the role of JAG1 and JAG2 in a MM in vivo model and primary patient samples. JAG1 and JAG2 protein expression represents a common feature in MM cell lines; therefore, we assessed their function through JAG1/2 conditional silencing in a MM xenograft model. We observed that JAG1 and JAG2 showed potential as therapeutic targets in MM, as their silencing resulted in a reduction in the tumor burden. Moreover, JAG1 and JAG2 protein expression in MM patients was positively correlated with the presence of MM cells in patients' bone marrow biopsies. Finally, taking advantage of the Multiple Myeloma Research Foundation (MMRF) CoMMpass global dataset, we showed that JAG2 gene expression level was a predictive biomarker associated with patients' overall survival and progression-free survival, independently from other main molecular or clinical features. Overall, these results strengthened the rationale for the development of a JAG1/2-tailored approach and the use of JAG2 as a predictive biomarker in MM.
    MeSH term(s) Humans ; Multiple Myeloma/drug therapy ; Multiple Myeloma/genetics ; Multiple Myeloma/pathology ; Intercellular Signaling Peptides and Proteins/genetics ; Intercellular Signaling Peptides and Proteins/metabolism ; Membrane Proteins/genetics ; Membrane Proteins/metabolism ; Receptors, Notch/metabolism ; Biomarkers ; Jagged-1 Protein/genetics ; Jagged-1 Protein/metabolism ; Ligands ; Tumor Microenvironment
    Chemical Substances Intercellular Signaling Peptides and Proteins ; Membrane Proteins ; Receptors, Notch ; Biomarkers ; Jagged-1 Protein ; Ligands
    Language English
    Publishing date 2023-09-26
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms241914558
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: EPIRETINAL FIBROSIS REMOVAL IN AN ARGUS II-IMPLANTED EYE: Histological Characteristics and Functional Results.

    Patelli, Fabio / Falleni, Monica / Colombo, Leonardo / Martinelli, Carla / Tosi, Delfina / Bulfamante, Gaetano / Rossetti, Luca

    Retina (Philadelphia, Pa.)

    2020  Volume 40, Issue 12, Page(s) 2403–2409

    Abstract: Purpose: 1) To investigate morphologic and histochemical characteristics of an epiretinal fibrosis removed in an Argus II-implanted eye; 2) to evaluate the Argus II function before and after the fibrosis removal, and 3) to compare morphologic and ... ...

    Abstract Purpose: 1) To investigate morphologic and histochemical characteristics of an epiretinal fibrosis removed in an Argus II-implanted eye; 2) to evaluate the Argus II function before and after the fibrosis removal, and 3) to compare morphologic and functional data.
    Methods: Fibrosis, which developed between the Argus II prosthesis and the retina two years after implant, was surgically removed. Its morphologic and histochemical characteristics were evaluated both in light and transmission electron microscopy, with special stains and immunohistochemistry. The Argus II function was evaluated during the follow-up before surgical removal and 1 month later.
    Results: Fibrosis was successfully removed. It was composed of a fibrotic tissue with spindle cells arranged in nodular aggregates with a symmetric distribution, mixed with an inflammatory infiltrate. Extra- and intracellular, irregular, small iron particles were found and confirmed ultrastructural characterization with degenerative cellular changes. The repositioned Argus II restored, and its function was partially nearly to normal values 1 month after surgery.
    Conclusion: Fibrosis can develop between the Argus II and the retina with increasing reduced function. Morphologic characteristics of the removed fibrosis suggested a pathogenesis based on an inflammatory process involved in a foreign body reaction with progressing connective tissue deposition leading to sclerosis. Adequate clinical follow-up is critical to successful removal of the fibrosis with reactivation of the Argus II function.
    MeSH term(s) Epiretinal Membrane/etiology ; Epiretinal Membrane/pathology ; Epiretinal Membrane/surgery ; Fibrosis/etiology ; Fibrosis/pathology ; Fibrosis/surgery ; Follow-Up Studies ; Humans ; Male ; Microscopy, Electron, Transmission ; Middle Aged ; Ophthalmologic Surgical Procedures ; Prosthesis Implantation ; Retina/pathology ; Retina/surgery ; Retinitis Pigmentosa/physiopathology ; Retinitis Pigmentosa/surgery ; Tomography, Optical Coherence ; Visual Prosthesis/adverse effects
    Language English
    Publishing date 2020-03-19
    Publishing country United States
    Document type Case Reports ; Journal Article
    ZDB-ID 603192-4
    ISSN 1539-2864 ; 0275-004X
    ISSN (online) 1539-2864
    ISSN 0275-004X
    DOI 10.1097/IAE.0000000000002780
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Therapeutic Effect of an Antibody-Derived Peptide in a

    Ottaviano, Emerenziana / Borghi, Elisa / Giovati, Laura / Falleni, Monica / Tosi, Delfina / Magliani, Walter / Morace, Giulia / Conti, Stefania / Ciociola, Tecla

    International journal of molecular sciences

    2021  Volume 22, Issue 20

    Abstract: The synthetic peptide T11F (TCRVDHRGLTF), with sequence identical to a fragment of the constant region of human IgM, and most of its alanine-substituted derivatives proved to possess a significant candidacidal activity in vitro. In this study, the ... ...

    Abstract The synthetic peptide T11F (TCRVDHRGLTF), with sequence identical to a fragment of the constant region of human IgM, and most of its alanine-substituted derivatives proved to possess a significant candidacidal activity in vitro. In this study, the therapeutic efficacy of T11F, D5A, the derivative most active in vitro, and F11A, characterized by a different conformation, was investigated in
    MeSH term(s) Animals ; Candida albicans/drug effects ; Candida albicans/pathogenicity ; Candidiasis/drug therapy ; Candidiasis/immunology ; Disease Models, Animal ; Hemocytes/drug effects ; Hemocytes/immunology ; Humans ; Immunoglobulin M/chemistry ; Larva/microbiology ; Microbial Viability/drug effects ; Moths/immunology ; Moths/microbiology ; Peptides/administration & dosage ; Peptides/chemistry ; Peptides/pharmacology ; Survival Analysis ; Treatment Outcome
    Chemical Substances Immunoglobulin M ; Peptides
    Language English
    Publishing date 2021-10-09
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms222010904
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Brainstem neuropathology in two cases of COVID-19: SARS-CoV-2 trafficking between brain and lung.

    Bulfamante, Gaetano / Bocci, Tommaso / Falleni, Monica / Campiglio, Laura / Coppola, Silvia / Tosi, Delfina / Chiumello, Davide / Priori, Alberto

    Journal of neurology

    2021  Volume 268, Issue 12, Page(s) 4486–4491

    Abstract: Introduction: SARS-CoV-2 might spread through the nervous system, reaching respiratory centers in the brainstem. Because we recently reported neurophysiological brainstem reflex abnormalities in COVID-19 patients, we here neuropathologically assessed ... ...

    Abstract Introduction: SARS-CoV-2 might spread through the nervous system, reaching respiratory centers in the brainstem. Because we recently reported neurophysiological brainstem reflex abnormalities in COVID-19 patients, we here neuropathologically assessed structural brainstem damage in two COVID-19 patients.
    Materials and methods: We assessed neuropathological features in two patients who died of COVID-19 and in two COVID-19 negative patients as controls. Neuronal damage and corpora amylacea (CA) numbers /mm
    Results: Autopsies showed normal gross brainstem anatomy. Histopathological examination demonstrated increased neuronal and CA damage in Covid-19 patients' medulla oblongata. Immunohistochemistry disclosed SARS-CoV-2 NP in brainstem neurons and glial cells, and in cranial nerves. Glial elements also exhibited a widespread increase in Iba-1 expression. Sars-Co-V2 was immunohistochemically detected in the vagus nerve fibers.
    Discussion: Neuropathologic evidence showing SARS-CoV-2 in the brainstem and medullary damage in the area of respiratory centers strongly suggests that the pathophysiology of COVID-19-related respiratory failure includes a neurogenic component. Sars-Co-V2 detection in the vagus nerve, argues for viral trafficking between brainstem and lung.
    MeSH term(s) Brain Stem/virology ; COVID-19 ; Humans ; Lung/virology ; Nervous System Diseases/virology ; SARS-CoV-2
    Language English
    Publishing date 2021-05-18
    Publishing country Germany
    Document type Case Reports ; Letter
    ZDB-ID 187050-6
    ISSN 1432-1459 ; 0340-5354 ; 0012-1037 ; 0939-1517 ; 1619-800X
    ISSN (online) 1432-1459
    ISSN 0340-5354 ; 0012-1037 ; 0939-1517 ; 1619-800X
    DOI 10.1007/s00415-021-10604-8
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article: Unexpected thymoma in a challenging case of hyperparathyroidism.

    Raveglia, Federico / De Pasquale, Loredana / Cioffi, Ugo / Ghilardi, Giorgio / De Simone, Matilde / Falleni, Monica / Baisi, Alessandro

    Clinical case reports

    2020  Volume 8, Issue 8, Page(s) 1425–1428

    Abstract: We report the case of a woman with primary hyperparathyroidism suspected of mediastinal ectopic parathyroid adenoma revealed to be a thymoma. Our aim was to focus on some possible criticisms in distinguishing between ectopic parathyroid and thymus. ...

    Abstract We report the case of a woman with primary hyperparathyroidism suspected of mediastinal ectopic parathyroid adenoma revealed to be a thymoma. Our aim was to focus on some possible criticisms in distinguishing between ectopic parathyroid and thymus.
    Language English
    Publishing date 2020-06-18
    Publishing country England
    Document type Case Reports
    ZDB-ID 2740234-4
    ISSN 2050-0904
    ISSN 2050-0904
    DOI 10.1002/ccr3.2842
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: CT colonography followed by elective surgery in patients with acute diverticulitis: a radiological-pathological correlation study.

    Flor, Nicola / Pickhardt, Perry J / Maconi, Giovanni / Panella, Silvia / Falleni, Monica / Merlo, Valeria / Di Leo, Giovanni

    Abdominal radiology (New York)

    2020  Volume 46, Issue 2, Page(s) 491–497

    Abstract: Purpose: To perform a radiologic-pathologic correlation analysis of sigmoid colon in patients undergoing pre-operative CT Colonography (CTC) after an episode of acute diverticulitis (AD).: Methods: Fifty-nine consecutive patients (31/28 M/F; 58 ± 13 ... ...

    Abstract Purpose: To perform a radiologic-pathologic correlation analysis of sigmoid colon in patients undergoing pre-operative CT Colonography (CTC) after an episode of acute diverticulitis (AD).
    Methods: Fifty-nine consecutive patients (31/28 M/F; 58 ± 13 years) underwent CTC 55 ± 18 days after AD, 8 ± 4 weeks before surgery. Thirty-seven patients (63%) underwent conventional abdominal CT at time of AD. An experienced blinded radiologist retrospectively analyzed all images: disease severity was graded according to the Ambrosetti classification on conventional CT and according to the diverticular disease severity score (DDSS) on CTC. A GI pathologist performed a dedicated analysis, evaluating the presence of acute and chronic inflammation, and fibrosis, using 0-3 point scale for each variable.
    Results: Of 59 patients, 41 (69%) had at least one previous AD episode; twenty-six patients (44%) had a complicated AD. DDSS was mild-moderate in 34/59 (58%), and severe in 25/59 (42%). All patients had chronic inflammation, while 90% had low-to-severe fibrosis. Patients with moderate/severe fibrosis were older than those with no/mild fibrosis (61 ± 13 versus 54 ± 13). We found a significant correlation between DDSS and chronic inflammation (p = 0.004), as well as DDSS and fibrosis (p = 0.005). Furthermore, fibrosis was correlated with complicated acute diverticulitis (p = 0.0.27), and with age (p = 0.067). At multivariate analysis, complicated diverticulitis was the best predictor of fibrosis (odds ratio 4.4). Patient age and DDSS were other independent predictors.
    Conclusion: DDSS-based assessment on preoperative CTC was a good predictor of chronic colonic inflammation and fibrosis. In addition, the presence of complicated diverticulitis on CT during the acute episode was most predictive of fibrosis.
    MeSH term(s) Acute Disease ; Colonography, Computed Tomographic ; Correlation of Data ; Diverticulitis ; Diverticulitis, Colonic/complications ; Diverticulitis, Colonic/diagnostic imaging ; Diverticulitis, Colonic/surgery ; Humans ; Retrospective Studies
    Language English
    Publishing date 2020-08-03
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2839786-1
    ISSN 2366-0058 ; 2366-004X
    ISSN (online) 2366-0058
    ISSN 2366-004X
    DOI 10.1007/s00261-020-02690-5
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Therapeutic Effect of an Antibody-Derived Peptide in a Galleria mellonella Model of Systemic Candidiasis

    Emerenziana Ottaviano / Elisa Borghi / Laura Giovati / Monica Falleni / Delfina Tosi / Walter Magliani / Giulia Morace / Stefania Conti / Tecla Ciociola

    International Journal of Molecular Sciences, Vol 22, Iss 10904, p

    2021  Volume 10904

    Abstract: The synthetic peptide T11F (TCRVDHRGLTF), with sequence identical to a fragment of the constant region of human IgM, and most of its alanine-substituted derivatives proved to possess a significant candidacidal activity in vitro. In this study, the ... ...

    Abstract The synthetic peptide T11F (TCRVDHRGLTF), with sequence identical to a fragment of the constant region of human IgM, and most of its alanine-substituted derivatives proved to possess a significant candidacidal activity in vitro. In this study, the therapeutic efficacy of T11F, D5A, the derivative most active in vitro, and F11A, characterized by a different conformation, was investigated in Galleria mellonella larvae infected with Candida albicans . A single injection of F11A and D5A derivatives, in contrast with T11F, led to a significant increase in survival of larvae injected with a lethal inoculum of C. albicans cells, in comparison with infected animals treated with saline. Peptide modulation of host immunity upon C. albicans infection was determined by hemocyte analysis and larval histology, highlighting a different immune stimulation by the studied peptides. F11A, particularly, was the most active in eliciting nodule formation, melanization and fat body activation, leading to a better control of yeast infection. Overall, the obtained data suggest a double role for F11A, able to simultaneously target the fungus and the host immune system, resulting in a more efficient pathogen clearance.
    Keywords antibody-derived peptides ; antifungal peptides ; immunomodulatory peptides ; Galleria mellonella ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Subject code 540
    Language English
    Publishing date 2021-10-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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