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  1. Article ; Online: Some antibodies can dampen antiviral defences in people with severe COVID.

    Gentili, Matteo / Hacohen, Nir

    Nature

    2021  Volume 591, Issue 7848, Page(s) 37–39

    MeSH term(s) Antibodies, Viral ; Antiviral Agents/therapeutic use ; COVID-19 ; Humans ; SARS-CoV-2
    Chemical Substances Antibodies, Viral ; Antiviral Agents
    Language English
    Publishing date 2021-03-02
    Publishing country England
    Document type News ; Comment
    ZDB-ID 120714-3
    ISSN 1476-4687 ; 0028-0836
    ISSN (online) 1476-4687
    ISSN 0028-0836
    DOI 10.1038/d41586-021-00352-0
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  2. Article: Spheroid size influences cellular senescence and angiogenic potential of mesenchymal stromal cell-derived soluble factors and extracellular vesicles.

    Rovere, Matteo / Reverberi, Daniele / Arnaldi, Pietro / Palamà, Maria Elisabetta Federica / Gentili, Chiara

    Frontiers in bioengineering and biotechnology

    2023  Volume 11, Page(s) 1297644

    Abstract: Introduction: ...

    Abstract Introduction:
    Language English
    Publishing date 2023-12-12
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2719493-0
    ISSN 2296-4185
    ISSN 2296-4185
    DOI 10.3389/fbioe.2023.1297644
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Microscale combinatorial stimulation of human myeloid cells reveals inflammatory priming by viral ligands.

    Reyes, Miguel / Leff, Samantha M / Gentili, Matteo / Hacohen, Nir / Blainey, Paul C

    Science advances

    2023  Volume 9, Issue 8, Page(s) eade5090

    Abstract: Cells sense a wide variety of signals and respond by adopting complex transcriptional states. Most single-cell profiling is carried out today at cellular baseline, blind to cells' potential spectrum of functional responses. Exploring the space of ... ...

    Abstract Cells sense a wide variety of signals and respond by adopting complex transcriptional states. Most single-cell profiling is carried out today at cellular baseline, blind to cells' potential spectrum of functional responses. Exploring the space of cellular responses experimentally requires access to a large combinatorial perturbation space. Single-cell genomics coupled with multiplexing techniques provide a useful tool for characterizing cell states across several experimental conditions. However, current multiplexing strategies require programmatic handling of many samples in macroscale arrayed formats, precluding their application in large-scale combinatorial analysis. Here, we introduce StimDrop, a method that combines antibody-based cell barcoding with parallel droplet processing to automatically formulate cell population × stimulus combinations in a microfluidic device. We applied StimDrop to profile the effects of 512 sequential stimulation conditions on human dendritic cells. Our results demonstrate that priming with viral ligands potentiates hyperinflammatory responses to a second stimulus, and show transcriptional signatures consistent with this phenomenon in myeloid cells of patients with severe COVID-19.
    MeSH term(s) Humans ; COVID-19 ; Myeloid Cells ; Ligands ; Lab-On-A-Chip Devices ; Single-Cell Analysis
    Chemical Substances Ligands
    Language English
    Publishing date 2023-02-24
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2810933-8
    ISSN 2375-2548 ; 2375-2548
    ISSN (online) 2375-2548
    ISSN 2375-2548
    DOI 10.1126/sciadv.ade5090
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Classification and functional characterization of regulators of intracellular STING trafficking identified by genome-wide optical pooled screening.

    Gentili, Matteo / Carlson, Rebecca J / Liu, Bingxu / Hellier, Quentin / Andrews, Jocelyn / Qin, Yue / Blainey, Paul C / Hacohen, Nir

    bioRxiv : the preprint server for biology

    2024  

    Abstract: STING is an innate immune sensor that traffics across many cellular compartments to carry out its function of detecting cyclic di-nucleotides and triggering defense processes. Mutations in factors that regulate this process are often linked to STING- ... ...

    Abstract STING is an innate immune sensor that traffics across many cellular compartments to carry out its function of detecting cyclic di-nucleotides and triggering defense processes. Mutations in factors that regulate this process are often linked to STING-dependent human inflammatory disorders. To systematically identify factors involved in STING trafficking, we performed a genome-wide optical pooled screen and examined the impact of genetic perturbations on intracellular STING localization. Based on subcellular imaging of STING protein and trafficking markers in 45 million cells perturbed with sgRNAs, we defined 464 clusters of gene perturbations with similar cellular phenotypes. A higher-dimensional focused optical pooled screen on 262 perturbed genes which assayed 11 imaging channels identified 73 finer phenotypic clusters. In a cluster containing USE1, a protein that mediates Golgi to ER transport, we found a gene of unknown function, C19orf25. Consistent with the known role of USE1, loss of C19orf25 enhanced STING signaling. Other clusters contained subunits of the HOPS, GARP and RIC1-RGP1 complexes. We show that HOPS deficiency delayed STING degradation and consequently increased signaling. Similarly, GARP/RIC1-RGP1 loss increased STING signaling by delaying STING exit from the Golgi. Our findings demonstrate that genome-wide genotype-phenotype maps based on high-content cell imaging outperform other screening approaches, and provide a community resource for mining for factors that impact STING trafficking as well as other cellular processes observable in our dataset.
    Language English
    Publishing date 2024-04-09
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2024.04.07.588166
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: A cell-free nanobody engineering platform rapidly generates SARS-CoV-2 neutralizing nanobodies.

    Chen, Xun / Gentili, Matteo / Hacohen, Nir / Regev, Aviv

    Nature communications

    2021  Volume 12, Issue 1, Page(s) 5506

    Abstract: Antibody engineering technologies face increasing demands for speed, reliability and scale. We develop CeVICA, a cell-free nanobody engineering platform that uses ribosome display for in vitro selection of nanobodies from a library of ... ...

    Abstract Antibody engineering technologies face increasing demands for speed, reliability and scale. We develop CeVICA, a cell-free nanobody engineering platform that uses ribosome display for in vitro selection of nanobodies from a library of 10
    MeSH term(s) Antibodies, Neutralizing/immunology ; Antibodies, Viral ; COVID-19/drug therapy ; Humans ; Protein Binding ; Protein Engineering ; Reproducibility of Results ; SARS-CoV-2/drug effects ; Single-Domain Antibodies/chemistry ; Single-Domain Antibodies/genetics ; Single-Domain Antibodies/pharmacology ; Spike Glycoprotein, Coronavirus
    Chemical Substances Antibodies, Neutralizing ; Antibodies, Viral ; Single-Domain Antibodies ; Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2
    Language English
    Publishing date 2021-09-17
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-021-25777-z
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: A cell-free nanobody engineering platform rapidly generates SARS-CoV-2 neutralizing nanobodies

    Xun Chen / Matteo Gentili / Nir Hacohen / Aviv Regev

    Nature Communications, Vol 12, Iss 1, Pp 1-

    2021  Volume 14

    Abstract: Faster, higher throughput antibody engineering methods are needed. Here the authors present CeVICA, a cell-free nanobody engineering platform using ribosome display and computational clustering analysis for in vitro selection; they use this to develop ... ...

    Abstract Faster, higher throughput antibody engineering methods are needed. Here the authors present CeVICA, a cell-free nanobody engineering platform using ribosome display and computational clustering analysis for in vitro selection; they use this to develop nanobodies against the RBD of SARS-CoV-2 spike protein.
    Keywords Science ; Q
    Language English
    Publishing date 2021-09-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

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  7. Article: A cell-free antibody engineering platform rapidly generates SARS-CoV-2 neutralizing antibodies.

    Chen, Xun / Gentili, Matteo / Hacohen, Nir / Regev, Aviv

    bioRxiv : the preprint server for biology

    2020  

    Abstract: Antibody engineering technologies face increasing demands for speed, reliability and scale. We developed CeVICA, a cell-free antibody engineering platform that integrates a novel generation method and design for camelid heavy-chain antibody VHH domain- ... ...

    Abstract Antibody engineering technologies face increasing demands for speed, reliability and scale. We developed CeVICA, a cell-free antibody engineering platform that integrates a novel generation method and design for camelid heavy-chain antibody VHH domain-based synthetic libraries, optimized
    Keywords covid19
    Language English
    Publishing date 2020-10-30
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2020.10.29.361287
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  8. Article ; Online: Bifunctional octadentate pseudopeptides as Zirconium-89 chelators for immuno-PET applications.

    Albanese, Valentina / Roccatello, Chiara / Pacifico, Salvatore / Guerrini, Remo / Preti, Delia / Gentili, Silvia / Tegoni, Matteo / Remelli, Maurizio / Bellotti, Denise / Amico, Jonathan / Gorgoni, Giancarlo / Cazzola, Emiliano

    EJNMMI radiopharmacy and chemistry

    2024  Volume 9, Issue 1, Page(s) 38

    Abstract: Background: Positron emission tomography (PET) is a highly sensitive method that provides fine resolution images, useful in the field of clinical diagnostics. In this context, Zirconium-89 (: Results: The main objective of this work was the design ... ...

    Abstract Background: Positron emission tomography (PET) is a highly sensitive method that provides fine resolution images, useful in the field of clinical diagnostics. In this context, Zirconium-89 (
    Results: The main objective of this work was the design and synthesis of a series of bifunctional octadentate pseudopeptides able to generate stable
    Conclusion: Combining solid phase and solution synthesis techniques, we identified novel
    Language English
    Publishing date 2024-05-06
    Publishing country England
    Document type Journal Article
    ISSN 2365-421X
    ISSN (online) 2365-421X
    DOI 10.1186/s41181-024-00263-1
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article: Niosomes Functionalized with a Synthetic Carbohydrate Binding Agent for Mannose-Targeted Doxorubicin Delivery.

    Burrini, Nastassja / D'Ambrosio, Mario / Gentili, Matteo / Giaquinto, Roberta / Settimelli, Veronica / Luceri, Cristina / Cirri, Marzia / Francesconi, Oscar

    Pharmaceutics

    2023  Volume 15, Issue 1

    Abstract: Niosomes are a potential tool for the development of active targeted drug delivery systems (DDS) for cancer therapy because of their excellent behaviour in encapsulating antitumorals and the possibility to easily functionalise their surface with ... ...

    Abstract Niosomes are a potential tool for the development of active targeted drug delivery systems (DDS) for cancer therapy because of their excellent behaviour in encapsulating antitumorals and the possibility to easily functionalise their surface with targeting agents. Recently, some of us developed a synthetic carbohydrate binding agent (CBA) able to target the mannosidic residues of high-mannose-type glycans overexpressed on the surface of several cancer cell lines, promoting their apoptosis. In this article, we modified the structure of this mannose receptor to obtain an amphiphilic analogue suitable for the functionalization of doxorubicin-based niosomes. Several niosomal formulations and preparation methods were investigated deeply to finally obtain functionalized niosomes suitable for parental administration, which were stable for over six months and able to encapsulate up to 85% of doxorubicin (DOXO). In vitro studies, carried out towards triple-negative cancer cells (MDA-MB231), overexpressing high-mannose-type glycans, showed a cytotoxic activity comparable to that of DOXO but with an appreciable increment in apoptosis given by the CBA. Moreover, niosomal formulation was observed to reduce doxorubicin-induced cytotoxicity towards normal cell lines of rat cardiomyocytes (H9C2). This study is propaedeutic to further in vivo investigations that can aim to shed light on the antitumoral activity and pharmacokinetics of the developed active targeted DDS.
    Language English
    Publishing date 2023-01-10
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2527217-2
    ISSN 1999-4923
    ISSN 1999-4923
    DOI 10.3390/pharmaceutics15010235
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  10. Article ; Online: Effects of Sulforaphane on SARS‑CoV‑2 infection and NF‑κB dependent expression of genes involved in the COVID‑19 'cytokine storm'.

    Gasparello, Jessica / Marzaro, Giovanni / Papi, Chiara / Gentili, Valentina / Rizzo, Roberta / Zurlo, Matteo / Scapoli, Chiara / Finotti, Alessia / Gambari, Roberto

    International journal of molecular medicine

    2023  Volume 52, Issue 3

    Abstract: Since its spread at the beginning of 2020, the coronavirus disease 2019 (COVID‑19) pandemic represents one of the major health problems. Despite the approval, testing, and worldwide distribution of anti‑severe acute respiratory syndrome coronavirus 2 ( ... ...

    Abstract Since its spread at the beginning of 2020, the coronavirus disease 2019 (COVID‑19) pandemic represents one of the major health problems. Despite the approval, testing, and worldwide distribution of anti‑severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) vaccines, the development of specific antiviral agents targeting the SARS‑CoV‑2 life cycle with high efficiency, and/or interfering with the associated 'cytokine storm', is highly required. A recent study, conducted by the authors' group indicated that sulforaphane (SFN) inhibits the expression of IL‑6 and IL‑8 genes induced by the treatment of IB3‑1 bronchial cells with a recombinant spike protein of SARS‑CoV‑2. In the present study, the ability of SFN to inhibit SARS‑CoV‑2 replication and the expression of pro‑inflammatory genes encoding proteins of the COVID‑19 'cytokine storm' was evaluated. SARS‑CoV‑2 replication was assessed in bronchial epithelial Calu‑3 cells. Moreover, SARS‑CoV‑2 replication and expression of pro‑inflammatory genes was evaluated by reverse transcription quantitative droplet digital PCR. The effects on the expression levels of NF‑κB were assessed by western blotting. Molecular dynamics simulations of NF‑kB/SFN interactions were conducted with Gromacs 2021.1 software under the Martini 2 CG force field. Computational studies indicated that i) SFN was stably bound with the NF‑κB monomer; ii) a ternary NF‑kB/SFN/DNA complex was formed; iii) the SFN interacted with both the protein and the nucleic acid molecules modifying the binding mode of the latter, and impairing the full interaction between the NF‑κB protein and the DNA molecule. This finally stabilized the inactive complex. Molecular studies demonstrated that SFN i) inhibits the SARS‑CoV‑2 replication in infected Calu‑3 cells, decreasing the production of the N‑protein coding RNA sequences, ii) decreased NF‑κB content in SARS‑CoV‑2 infected cells and inhibited the expression of NF‑kB‑dependent IL‑1β and IL‑8 gene expression. The data obtained in the present study demonstrated inhibitory effects of SFN on the SARS‑CoV‑2 life cycle and on the expression levels of the pro‑inflammatory genes, sustaining the possible use of SFN in the management of patients with COVID‑19.
    MeSH term(s) Humans ; COVID-19 ; NF-kappa B/genetics ; Interleukin-8 ; SARS-CoV-2 ; Isothiocyanates/pharmacology ; Isothiocyanates/therapeutic use ; DNA
    Chemical Substances sulforaphane (GA49J4310U) ; NF-kappa B ; Interleukin-8 ; Isothiocyanates ; DNA (9007-49-2)
    Language English
    Publishing date 2023-07-21
    Publishing country Greece
    Document type Journal Article
    ZDB-ID 1444428-8
    ISSN 1791-244X ; 1107-3756
    ISSN (online) 1791-244X
    ISSN 1107-3756
    DOI 10.3892/ijmm.2023.5279
    Database MEDical Literature Analysis and Retrieval System OnLINE

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