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  1. Article ; Online: Programmed Cell Death in Health and Disease.

    Gibellini, Lara / Moro, Loredana

    Cells

    2021  Volume 10, Issue 7

    Abstract: Programmed cell death is a conserved evolutionary process of cell suicide that is central to the development and integrity of eukaryotic organisms [ ... ]. ...

    Abstract Programmed cell death is a conserved evolutionary process of cell suicide that is central to the development and integrity of eukaryotic organisms [...].
    MeSH term(s) Animals ; Apoptosis/drug effects ; Biological Products/pharmacology ; Caenorhabditis elegans/drug effects ; Caspase 2/metabolism ; Disease ; Health ; Humans ; Mitochondria/drug effects ; Mitochondria/metabolism ; Neoplasms/pathology ; Nerve Degeneration/pathology
    Chemical Substances Biological Products ; Caspase 2 (EC 3.4.22.-)
    Language English
    Publishing date 2021-07-13
    Publishing country Switzerland
    Document type Editorial ; Introductory Journal Article
    ZDB-ID 2661518-6
    ISSN 2073-4409 ; 2073-4409
    ISSN (online) 2073-4409
    ISSN 2073-4409
    DOI 10.3390/cells10071765
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Circulating and Tumor-Associated Neutrophils in the Era of Immune Checkpoint Inhibitors: Dynamics, Phenotypes, Metabolism, and Functions.

    Gibellini, Lara / Borella, Rebecca / Santacroce, Elena / Serattini, Eugenia / Boraldi, Federica / Quaglino, Daniela / Aramini, Beatrice / De Biasi, Sara / Cossarizza, Andrea

    Cancers

    2023  Volume 15, Issue 13

    Abstract: Neutrophils are the most abundant myeloid cells in the blood and are a considerable immunological component of the tumor microenvironment. However, their functional importance has often been ignored, as they have always been considered a mono-dimensional ...

    Abstract Neutrophils are the most abundant myeloid cells in the blood and are a considerable immunological component of the tumor microenvironment. However, their functional importance has often been ignored, as they have always been considered a mono-dimensional population of terminally differentiated, short-living cells. During the last decade, the use of cutting-edge, single-cell technologies has revolutionized the classical view of these cells, unmasking their phenotypic and functional heterogeneity. In this review, we summarize the emerging concepts in the field of neutrophils in cancer, by reviewing the recent literature on the heterogeneity of both circulating neutrophils and tumor-associated neutrophils, as well as their possible significance in tumor prognosis and resistance to immune checkpoint inhibitors.
    Language English
    Publishing date 2023-06-24
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers15133327
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Mitophagy and Oxidative Stress: The Role of Aging.

    De Gaetano, Anna / Gibellini, Lara / Zanini, Giada / Nasi, Milena / Cossarizza, Andrea / Pinti, Marcello

    Antioxidants (Basel, Switzerland)

    2021  Volume 10, Issue 5

    Abstract: Mitochondrial dysfunction is a hallmark of aging. Dysfunctional mitochondria are recognized and degraded by a selective type of macroautophagy, named mitophagy. One of the main factors contributing to aging is oxidative stress, and one of the early ... ...

    Abstract Mitochondrial dysfunction is a hallmark of aging. Dysfunctional mitochondria are recognized and degraded by a selective type of macroautophagy, named mitophagy. One of the main factors contributing to aging is oxidative stress, and one of the early responses to excessive reactive oxygen species (ROS) production is the induction of mitophagy to remove damaged mitochondria. However, mitochondrial damage caused at least in part by chronic oxidative stress can accumulate, and autophagic and mitophagic pathways can become overwhelmed. The imbalance of the delicate equilibrium among mitophagy, ROS production and mitochondrial damage can start, drive, or accelerate the aging process, either in physiological aging, or in pathological age-related conditions, such as Alzheimer's and Parkinson's diseases. It remains to be determined which is the prime mover of this imbalance, i.e., whether it is the mitochondrial damage caused by ROS that initiates the dysregulation of mitophagy, thus activating a vicious circle that leads to the reduced ability to remove damaged mitochondria, or an alteration in the regulation of mitophagy leading to the excessive production of ROS by damaged mitochondria.
    Language English
    Publishing date 2021-05-17
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2704216-9
    ISSN 2076-3921
    ISSN 2076-3921
    DOI 10.3390/antiox10050794
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Gene Expression Analysis of T-Cells by Single-Cell RNA-Seq.

    Lo Tartaro, Domenico / De Biasi, Sara / Forcato, Mattia / Gibellini, Lara / Cossarizza, Andrea

    Methods in molecular biology (Clifton, N.J.)

    2021  Volume 2285, Page(s) 277–296

    Abstract: During the last decade, the rapid progress in the development of next-generation sequencing (NGS) technologies has provided relevant insights into complex biological systems, ranging from cancer genomics to microbiology. Among NGS technologies, single- ... ...

    Abstract During the last decade, the rapid progress in the development of next-generation sequencing (NGS) technologies has provided relevant insights into complex biological systems, ranging from cancer genomics to microbiology. Among NGS technologies, single-cell RNA sequencing is currently used to decipher the complex heterogeneity of several biological samples, including T cells. Even if this technique requires specialized equipment and expertise, nowadays it is broadly applied in research. In this chapter, we will provide an optimized protocol for the isolation of T cells and the preparation of RNA sequencing libraries by using droplet digital technology (ddSEQ, Bio-Rad Laboratories). We will also illustrate a guide to the main steps of data processing and options for data interpretation. This protocol will support users in building a single-cell experimental framework, from sample preparation to data interpretation.
    MeSH term(s) CD8-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/metabolism ; Cell Separation ; Gene Expression Regulation ; Gene Library ; Humans ; Lab-On-A-Chip Devices ; Microfluidic Analytical Techniques/instrumentation ; RNA-Seq ; Research Design ; Single-Cell Analysis ; Workflow
    Language English
    Publishing date 2021-04-30
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 1940-6029
    ISSN (online) 1940-6029
    DOI 10.1007/978-1-0716-1311-5_22
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Finding predictive factors for immunotherapy in metastatic renal-cell carcinoma: What are we looking for?

    Guida, Annalisa / Sabbatini, Roberto / Gibellini, Lara / De Biasi, Sara / Cossarizza, Andrea / Porta, Camillo

    Cancer treatment reviews

    2021  Volume 94, Page(s) 102157

    Abstract: A major breakthrough in cancer immunotherapy was the development of monoclonal antibodies targeting inhibitory immune checkpoint proteins. This approach demonstrated significant antitumor activity and efficacy in different cancer types, including ... ...

    Abstract A major breakthrough in cancer immunotherapy was the development of monoclonal antibodies targeting inhibitory immune checkpoint proteins. This approach demonstrated significant antitumor activity and efficacy in different cancer types, including metastatic renal cell carcinoma (mRCC). In the majority of patients, this drug is able to restore the patient's tumour-specific T-cell-mediated response thus improving both overall survival and objective response rate. However, a lack of clinical response occurs in a number of patients, raising questions about how to predict and increase the number of patients who receive long-term clinical benefit from immune checkpoint therapy or not. The aim of this review is to summarize available data about immune biomarkers in patients with mRCC treated with immunotherapy.
    MeSH term(s) Animals ; Antineoplastic Agents, Immunological/administration & dosage ; Antineoplastic Combined Chemotherapy Protocols/administration & dosage ; B7-H1 Antigen/biosynthesis ; B7-H1 Antigen/immunology ; Carcinoma, Renal Cell/drug therapy ; Carcinoma, Renal Cell/genetics ; Carcinoma, Renal Cell/immunology ; Carcinoma, Renal Cell/pathology ; Clinical Trials, Phase III as Topic ; Humans ; Immune Checkpoint Inhibitors/administration & dosage ; Kidney Neoplasms/drug therapy ; Kidney Neoplasms/genetics ; Kidney Neoplasms/immunology ; Kidney Neoplasms/pathology ; Predictive Value of Tests ; Randomized Controlled Trials as Topic ; Transcriptome ; Xenograft Model Antitumor Assays
    Chemical Substances Antineoplastic Agents, Immunological ; B7-H1 Antigen ; CD274 protein, human ; Immune Checkpoint Inhibitors
    Language English
    Publishing date 2021-02-01
    Publishing country Netherlands
    Document type Journal Article ; Review
    ZDB-ID 125102-8
    ISSN 1532-1967 ; 0305-7372
    ISSN (online) 1532-1967
    ISSN 0305-7372
    DOI 10.1016/j.ctrv.2021.102157
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Advances and Challenges in Sepsis Management: Modern Tools and Future Directions.

    Santacroce, Elena / D'Angerio, Miriam / Ciobanu, Alin Liviu / Masini, Linda / Lo Tartaro, Domenico / Coloretti, Irene / Busani, Stefano / Rubio, Ignacio / Meschiari, Marianna / Franceschini, Erica / Mussini, Cristina / Girardis, Massimo / Gibellini, Lara / Cossarizza, Andrea / De Biasi, Sara

    Cells

    2024  Volume 13, Issue 5

    Abstract: Sepsis, a critical condition marked by systemic inflammation, profoundly impacts both innate and adaptive immunity, often resulting in lymphopenia. This immune alteration can spare regulatory T cells (Tregs) but significantly affects other lymphocyte ... ...

    Abstract Sepsis, a critical condition marked by systemic inflammation, profoundly impacts both innate and adaptive immunity, often resulting in lymphopenia. This immune alteration can spare regulatory T cells (Tregs) but significantly affects other lymphocyte subsets, leading to diminished effector functions, altered cytokine profiles, and metabolic changes. The complexity of sepsis stems not only from its pathophysiology but also from the heterogeneity of patient responses, posing significant challenges in developing universally effective therapies. This review emphasizes the importance of phenotyping in sepsis to enhance patient-specific diagnostic and therapeutic strategies. Phenotyping immune cells, which categorizes patients based on clinical and immunological characteristics, is pivotal for tailoring treatment approaches. Flow cytometry emerges as a crucial tool in this endeavor, offering rapid, low cost and detailed analysis of immune cell populations and their functional states. Indeed, this technology facilitates the understanding of immune dysfunctions in sepsis and contributes to the identification of novel biomarkers. Our review underscores the potential of integrating flow cytometry with omics data, machine learning and clinical observations to refine sepsis management, highlighting the shift towards personalized medicine in critical care. This approach could lead to more precise interventions, improving outcomes in this heterogeneously affected patient population.
    MeSH term(s) Humans ; Adaptive Immunity ; Biomarkers ; Inflammation ; Precision Medicine/methods ; Sepsis
    Chemical Substances Biomarkers
    Language English
    Publishing date 2024-03-02
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2661518-6
    ISSN 2073-4409 ; 2073-4409
    ISSN (online) 2073-4409
    ISSN 2073-4409
    DOI 10.3390/cells13050439
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Immunosenescence and vaccine efficacy revealed by immunometabolic analysis of SARS-CoV-2-specific cells in multiple sclerosis patients.

    De Biasi, Sara / Lo Tartaro, Domenico / Neroni, Anita / Rau, Moritz / Paschalidis, Nikolaos / Borella, Rebecca / Santacroce, Elena / Paolini, Annamaria / Gibellini, Lara / Ciobanu, Alin Liviu / Cuccorese, Michela / Trenti, Tommaso / Rubio, Ignacio / Vitetta, Francesca / Cardi, Martina / Argüello, Rafael José / Ferraro, Diana / Cossarizza, Andrea

    Nature communications

    2024  Volume 15, Issue 1, Page(s) 2752

    Abstract: Disease-modifying therapies (DMT) administered to patients with multiple sclerosis (MS) can influence immune responses to SARS-CoV-2 and vaccine efficacy. However, data on the detailed phenotypic, functional and metabolic characteristics of antigen (Ag)- ... ...

    Abstract Disease-modifying therapies (DMT) administered to patients with multiple sclerosis (MS) can influence immune responses to SARS-CoV-2 and vaccine efficacy. However, data on the detailed phenotypic, functional and metabolic characteristics of antigen (Ag)-specific cells following the third dose of mRNA vaccine remain scarce. Here, using flow cytometry and 45-parameter mass cytometry, we broadly investigate the phenotype, function and the single-cell metabolic profile of SARS-CoV-2-specific T and B cells up to 8 months after the third dose of mRNA vaccine in a cohort of 94 patients with MS treated with different DMT, including cladribine, dimethyl fumarate, fingolimod, interferon, natalizumab, teriflunomide, rituximab or ocrelizumab. Almost all patients display functional immune response to SARS-CoV-2. Different metabolic profiles characterize antigen-specific-T and -B cell response in fingolimod- and natalizumab-treated patients, whose immune response differs from all the other MS treatments.
    MeSH term(s) Humans ; Multiple Sclerosis ; Immunosuppressive Agents/therapeutic use ; Fingolimod Hydrochloride/therapeutic use ; SARS-CoV-2 ; Natalizumab/therapeutic use ; Vaccine Efficacy ; mRNA Vaccines ; COVID-19/prevention & control ; Immunosenescence
    Chemical Substances Immunosuppressive Agents ; Fingolimod Hydrochloride (G926EC510T) ; Natalizumab ; mRNA Vaccines
    Language English
    Publishing date 2024-03-29
    Publishing country England
    Document type Journal Article
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-024-47013-0
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Differential Expression of Lonp1 Isoforms in Cancer Cells.

    Zanini, Giada / Selleri, Valentina / De Gaetano, Anna / Gibellini, Lara / Malerba, Mara / Mattioli, Anna Vittoria / Nasi, Milena / Apostolova, Nadezda / Pinti, Marcello

    Cells

    2022  Volume 11, Issue 23

    Abstract: Lonp1 is a mitochondrial protease that degrades oxidized and damaged proteins, assists protein folding, and contributes to the maintenance of mitochondrial DNA. A higher expression of LonP1 has been associated with higher tumour aggressiveness. Besides ... ...

    Abstract Lonp1 is a mitochondrial protease that degrades oxidized and damaged proteins, assists protein folding, and contributes to the maintenance of mitochondrial DNA. A higher expression of LonP1 has been associated with higher tumour aggressiveness. Besides the full-length isoform (ISO1), we identified two other isoforms of Lonp1 in humans, resulting from alternative splicing: Isoform-2 (ISO2) lacking aa 42-105 and isoform-3 (ISO3) lacking aa 1-196. An inspection of the public database TSVdb showed that ISO1 was upregulated in lung, bladder, prostate, and breast cancer, ISO2 in all the cancers analysed (including rectum, colon, cervical, bladder, prostate, breast, head, and neck), ISO3 did not show significant changes between cancer and normal tissue. We overexpressed ISO1, ISO2, and ISO3 in SW620 cells and found that the ISO1 isoform was exclusively mitochondrial, ISO2 was present in the organelle and in the cytoplasm, and ISO3 was exclusively cytoplasmatic. The overexpression of ISO1 and, at a letter extent, of ISO2 enhanced basal, ATP-linked, and maximal respiration without altering the mitochondria number or network, mtDNA amount. or mitochondrial dynamics. A higher extracellular acidification rate was observed in ISO1 and ISO2, overexpressing cells, suggesting an increase in glycolysis. Cells overexpressing the different isoforms did not show a difference in the proliferation rate but showed a great increase in anchorage-independent growth. ISO1 and ISO2, but not ISO3, determined an upregulation of EMT-related proteins, which appeared unrelated to higher mitochondrial ROS production, nor due to the activation of the MEK ERK pathway, but rather to global metabolic reprogramming of cells.
    Language English
    Publishing date 2022-12-06
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2661518-6
    ISSN 2073-4409 ; 2073-4409
    ISSN (online) 2073-4409
    ISSN 2073-4409
    DOI 10.3390/cells11233940
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: A Comprehensive Analysis of Cytokine Network in Centenarians.

    Pinti, Marcello / Gibellini, Lara / Lo Tartaro, Domenico / De Biasi, Sara / Nasi, Milena / Borella, Rebecca / Fidanza, Lucia / Neroni, Anita / Troiano, Leonarda / Franceschi, Claudio / Cossarizza, Andrea

    International journal of molecular sciences

    2023  Volume 24, Issue 3

    Abstract: Cytokines have been investigated extensively in elderly people, with conflicting results. We performed a comprehensive analysis of the plasma levels of 62 cytokines and growth factors involved in the regulation of the immune system, in healthy ... ...

    Abstract Cytokines have been investigated extensively in elderly people, with conflicting results. We performed a comprehensive analysis of the plasma levels of 62 cytokines and growth factors involved in the regulation of the immune system, in healthy centenarians, and middle-aged controls. We confirmed the previously observed increase in the levels of several pro-inflammatory cytokines, such as TNF-α and IL-6, and found that several other cytokines, directly or indirectly involved in inflammation (such as IFN-α, IL-23, CCL-5), were present at higher levels in centenarians. We did not observe any increase in the levels of anti-inflammatory cytokines, with the notable exception of the Th2-shifting cytokine IL-19. No relevant difference was observed in cytokines regulating T cell immunity. Several growth factors having a role in regulating immunity, such as G-CSF, GM-CSF, EGF, and VEGF, were upregulated in centenarians, too. Principal component analysis of the cytokine dataset showed that pro and anti-inflammatory cytokines were the variables that contributed the most to the variability of the data we observed.
    MeSH term(s) Middle Aged ; Aged, 80 and over ; Humans ; Aged ; Cytokines/metabolism ; Centenarians ; Inflammation ; Anti-Inflammatory Agents
    Chemical Substances Cytokines ; Anti-Inflammatory Agents
    Language English
    Publishing date 2023-02-01
    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/ijms24032719
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Differential Expression of Lonp1 Isoforms in Cancer Cells

    Giada Zanini / Valentina Selleri / Anna De Gaetano / Lara Gibellini / Mara Malerba / Anna Vittoria Mattioli / Milena Nasi / Nadezda Apostolova / Marcello Pinti

    Cells, Vol 11, Iss 3940, p

    2022  Volume 3940

    Abstract: Lonp1 is a mitochondrial protease that degrades oxidized and damaged proteins, assists protein folding, and contributes to the maintenance of mitochondrial DNA. A higher expression of LonP1 has been associated with higher tumour aggressiveness. Besides ... ...

    Abstract Lonp1 is a mitochondrial protease that degrades oxidized and damaged proteins, assists protein folding, and contributes to the maintenance of mitochondrial DNA. A higher expression of LonP1 has been associated with higher tumour aggressiveness. Besides the full-length isoform (ISO1), we identified two other isoforms of Lonp1 in humans, resulting from alternative splicing: Isoform-2 (ISO2) lacking aa 42-105 and isoform-3 (ISO3) lacking aa 1-196. An inspection of the public database TSVdb showed that ISO1 was upregulated in lung, bladder, prostate, and breast cancer, ISO2 in all the cancers analysed (including rectum, colon, cervical, bladder, prostate, breast, head, and neck), ISO3 did not show significant changes between cancer and normal tissue. We overexpressed ISO1, ISO2, and ISO3 in SW620 cells and found that the ISO1 isoform was exclusively mitochondrial, ISO2 was present in the organelle and in the cytoplasm, and ISO3 was exclusively cytoplasmatic. The overexpression of ISO1 and, at a letter extent, of ISO2 enhanced basal, ATP-linked, and maximal respiration without altering the mitochondria number or network, mtDNA amount. or mitochondrial dynamics. A higher extracellular acidification rate was observed in ISO1 and ISO2, overexpressing cells, suggesting an increase in glycolysis. Cells overexpressing the different isoforms did not show a difference in the proliferation rate but showed a great increase in anchorage-independent growth. ISO1 and ISO2, but not ISO3, determined an upregulation of EMT-related proteins, which appeared unrelated to higher mitochondrial ROS production, nor due to the activation of the MEK ERK pathway, but rather to global metabolic reprogramming of cells.
    Keywords Lon protease ; mitochondria ; SW620 ; mitochondrial DNA ; Biology (General) ; QH301-705.5
    Subject code 570
    Language English
    Publishing date 2022-12-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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