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Cell Biology: State-of-the-Art and Perspectives in Italy 2024

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A special issue of Cells (ISSN 2073-4409).

Deadline for manuscript submissions: closed (31 December 2024) | Viewed by 18921

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Dr. Vincenzo Carafa

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Department of Precision Medicine, University of Campania Luigi Vanvitelli, 80138 Napoli, Italy
Interests: programmed cell death; apoptosis; leukaemia; epigenetic; acetylation; sirtuins
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Special Issue Information

Dear Colleagues,

Welcome to the second edition of the Special Issue "Cell Biology: State of the Art and Perspectives in Italy." Building upon the success of our inaugural edition, we are delighted to present this follow-up collection of cutting-edge research and perspectives in the field of cell biology, with a focus on Italy.

In our rapidly evolving scientific landscape, cell biology remains at the forefront of exploration and discovery. This Special Issue serves as a platform to showcase the latest advancements and insights emerging from the vibrant scientific community in Italy. It brings together a diverse range of contributions from researchers, scholars, and experts who are dedicated to unraveling the mysteries of cellular life.

The primary objective of this Special Issue is to continue fostering collaboration, knowledge exchange, and innovation within the field of cell biology. As we delve deeper into the intricate workings of cells, we uncover novel pathways, mechanisms, and technologies that have profound implications for various domains, including medicine, biotechnology, and environmental sciences. Moreover, this edition aims to highlight the interdisciplinary nature of cell biology and its integral role in addressing some of the most pressing global challenges. Potential topics include but are not limited to the following research areas:

Cell structure: organelles, cytoskeleton, cell membrane, capsule, flagella, etc.;
Cell physiology: cell growth, metabolism, protein synthesis, division, movement of proteins, active/passive transport, intra- and extracellular signaling, adhesion, DNA repair, etc.;
Cell movement and motility;
Autophagy;
Apoptosis;
Cell aging;
Cell techniques: cell and tissue culture, isolation, and fractionation of cells; immunocytochemistry (ICC); in situ hybridization (ISH); transfection; and optogenetics;
Cell growth and differentiation;
Hematopoiesis and stem cells;
Cancer stem cells;
Genetic disorders;
CAR-T cell research.

We invite researchers to contribute their original research articles, reviews, and perspectives, shedding light on both the fundamental aspects of cell biology and their practical applications. By doing so, we aim to provide a comprehensive overview of the state of cell biology research in Italy in 2024 and to inspire future breakthroughs and collaborations.

Thank you for your participation in this exciting journey of discovery, and we look forward to sharing the remarkable contributions that await with this second edition of "Cell Biology: State of the Art and Perspectives in Italy."

Dr. Vincenzo Carafa
Guest Editor

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Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cells is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

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Related Special Issue

Cell Biology: State-of-the-Art and Perspectives in Italy in Cells (7 articles)

Published Papers (10 papers)

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Research

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15 pages, 1032 KiB

Open AccessArticle

Patients with Irritable Bowel Syndrome Exhibit Aberrant Expression of Endogenous Retroviruses and SETDB1

by Pier-Angelo Tovo, Davide Giuseppe Ribaldone, Gian Paolo Caviglia, Cristina Calvi, Paola Montanari, Marco Tizzani, Demis Pitoni, Simone Frara, Elisa Tribocco, Stefano Gambarino, Marta Guariglia, Ilaria Galliano and Massimiliano Bergallo

Cells 2025, 14(3), 196; https://doi.org/10.3390/cells14030196 - 29 Jan 2025

Viewed by 977

Abstract

Irritable bowel syndrome (IBS) is a common disease, whose etiopathogenesis is poorly understood. Human endogenous retroviruses (HERVs) originate from ancient infections of germinal cells and represent 8% of our DNA. Most HERVs have become defective due to the accumulated mutations; some can, however, still be activated, and their altered expressions have been associated with a number of chronic inflammatory and immune-mediated disorders, including gastrointestinal diseases. Retroviral transcription is modulated by TRIM28 and SETDB1, which also participate in the regulation of epigenetic mechanisms and in shaping the immune system. Expressions of HERVs and TRIM28/SETDB1 have not been investigated in patients affected by IBS. Using a PCR real-time Taqman amplification assay, we explored the RNA levels of HERV-H-pol, HERV-K-pol, and HERV-W-pol; syncytin 1 (SYN1), SYN2, and HERV-W-env; and TRIM28 and SETDB1 in the peripheral blood of 37 IBS patients and healthy controls (HCs) of similar age. The transcript levels were higher in IBS patients than in HCs for all HERVs except for HERV-W-pol, with significant p-values for HERV-H-pol, HERV-K-pol, and SYN1 and borderline p-values for SYN2 and HERV-W-env. The RNA levels of SETDB1 were significantly enhanced in IBS patients, while those of TRIM28 were in the normal range. Patients with severe disease had significant upregulation of SETDB1 compared to those with mild or moderate symptoms. These findings suggest that overexpression of HERVs and SETDB1 may contribute to the development of IBS and open the way to innovative therapeutic strategies. Full article

(This article belongs to the Special Issue Cell Biology: State-of-the-Art and Perspectives in Italy 2024)

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27 pages, 7008 KiB

Open AccessArticle

Characterization of the Astrocyte Calcium Response to Norepinephrine in the Ventral Tegmental Area

by Michele Speggiorin, Angela Chiavegato, Micaela Zonta and Marta Gómez-Gonzalo

Cells 2025, 14(1), 24; https://doi.org/10.3390/cells14010024 - 30 Dec 2024

Cited by 1 | Viewed by 3962

Abstract

Astrocytes from different brain regions respond with Ca²⁺ elevations to the catecholamine norepinephrine (NE). However, whether this noradrenergic-mediated signaling is present in astrocytes from the ventral tegmental area (VTA), a dopaminergic circuit receiving noradrenergic inputs, has not yet been investigated. To fill in this gap, we applied a pharmacological approach along with two-photon microscopy and an AAV strategy to express a genetically encoded calcium indicator in VTA astrocytes. We found that VTA astrocytes from both female and male young adult mice showed a strong Ca²⁺ response to NE at both soma and processes. Our results revealed that Gq-coupled α1 adrenergic receptors, which elicit the production of IP3, are the main mediators of the astrocyte response. In mice lacking the IP3 receptor type-2 (IP3R2^−/− mice), we found that the astrocyte response to NE, even if reduced, is still present. We also found that in IP3R2^−/− astrocytes, the residual Ca²⁺ elevations elicited by NE depend on the release of Ca²⁺ from the endoplasmic reticulum, through IP3Rs different from IP3R2. In conclusion, our results reveal VTA astrocytes as novel targets of the noradrenergic signaling, opening to new interpretations of the cellular and molecular mechanisms that mediate the NE effects in the VTA. Full article

(This article belongs to the Special Issue Cell Biology: State-of-the-Art and Perspectives in Italy 2024)

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14 pages, 3134 KiB

Open AccessArticle

Enhancing Gene Delivery in NB-4 Cells: Overcoming Transduction and Selection Challenges

by Stefano Leto, Sonakshi Gehlot, Bhavwanti Sheth, Stefano Ratti, Lucia Manzoli, Nullin Divecha and Roberta Fiume

Cells 2024, 13(22), 1849; https://doi.org/10.3390/cells13221849 - 8 Nov 2024

Viewed by 1264

Abstract

Efficient gene transduction and cell viability are critical factors in genetic manipulation for research and therapeutic purposes. In this study, we explored the challenges associated with transducing the NB-4 cell line, a well-established model for acute promyelocytic leukemia (APL), using lentiviral vectors. While the initial transduction efficiency in NB-4 cells reached approximately 30%, we observed a significant decrease in cell viability, a phenomenon not observed in other acute leukemia cell lines such as THP-1 cells. We identified that this toxicity could be mitigated by purifying viral particles through ultracentrifugation or polyethylene glycol (PEG) precipitation, indicating that toxic substances, potentially secondary metabolites released by HEK293, could be responsible for the cell death. Nevertheless, cell selection by puromycin was still ineffective; crucially, we discovered that the human phosphoglycerate kinase (hPGK) promoter, commonly used in the PLKO1 vector, may become silenced in NB-4 cells, preventing effective selection with puromycin. By replacing the hPGK promoter with the elongation factor-1 alpha (EF1α) promoter, we successfully achieved high transduction efficiency and robust selection, demonstrating the potential for this modified vector system to facilitate genetic studies in APL models. These findings provide important insights into optimizing gene transduction protocols not only for NB-4 cells but also for other challenging cell lines, offering a refined approach for gene delivery and selection in cell models. Full article

(This article belongs to the Special Issue Cell Biology: State-of-the-Art and Perspectives in Italy 2024)

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21 pages, 12979 KiB

Open AccessArticle

Lactate-Induced HBEGF Shedding and EGFR Activation: Paving the Way to a New Anticancer Therapeutic Opportunity

by Valentina Rossi, Alejandro Hochkoeppler, Marzia Govoni and Giuseppina Di Stefano

Cells 2024, 13(18), 1533; https://doi.org/10.3390/cells13181533 - 13 Sep 2024

Viewed by 1496

Abstract

Cancer cells can release EGF-like peptides, acquiring the capacity of autocrine stimulation via EGFR-mediated signaling. One of these peptides (HBEGF) was found to be released from a membrane-bound precursor protein and is critically implicated in the proliferative potential of cancer cells. We observed that the increased lactate levels characterizing neoplastic tissues can induce the release of uPA, a protease promoting HBEGF shedding. This effect led to EGFR activation and increased ERK1/2 phosphorylation. Since EGFR-mediated signaling potentiates glycolytic metabolism, this phenomenon can induce a self-sustaining deleterious loop, favoring tumor growth. A well characterized HBEGF inhibitor is CRM197, a single-site variant of diphtheria toxin. We observed that, when administered individually, CRM197 did not trigger evident antineoplastic effects. However, its association with a uPA inhibitor caused dampening of EGFR-mediated signaling and apoptosis induction. Overall, our study highlights that the increased glycolytic metabolism and lactate production can foster the activated state of EGFR receptor and suggests that the inhibition of EGFR-mediated signaling can be attempted by means of CRM197 administered with an appropriate protease inhibitor. This attempt could help in overcoming the problem of the acquired resistance to the conventionally used EGFR inhibitors. Full article

(This article belongs to the Special Issue Cell Biology: State-of-the-Art and Perspectives in Italy 2024)

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13 pages, 1054 KiB

Open AccessArticle

Impact of Neuroendocrine Differentiation (NED) on Enzalutamide and Abiraterone Efficacy in Metastatic Castration-Resistant Prostate Cancer (mCRPC): A Retrospective Analysis

by Giovanni Farinea, Mariangela Calabrese, Federica Carfì, Isabella Saporita, Stefano Poletto, Marco Donatello Delcuratolo, Fabio Turco, Marco Audisio, Francesco Rosario Di Stefano, Marcello Tucci and Consuelo Buttigliero

Cells 2024, 13(16), 1396; https://doi.org/10.3390/cells13161396 - 22 Aug 2024

Viewed by 1683

Abstract

Neuroendocrine differentiation (NED) represents a possible androgen receptor pathway inhibitors (ARPI) resistance mechanism in metastatic castration resistance prostate cancer (mCRPC). As mCRPC with NED has been excluded from clinical trials evaluating ARPI efficacy, this study investigates the prognostic impact of NED in mCRPC patients treated with ARPIs. Methods: We retrospectively analyzed 327 mCRPC patient data treated with Enzalutamide or Abiraterone in the first and second or successive lines of treatment. NED was assessed using prostate biopsy samples through immunohistochemical staining. Results: NED was confirmed in 32/327 (9.8%) mCRPC patients. In the overall population, mCRPC with NED showed worse PFS (4.38 vs. 11.48 months HR 2.505 [1.71–3.68] p < 0.05), disease control rate (DCR), and PSA response. In the first line setting, mCRPC with NED demonstrated worse PFS (8.5 vs. 14.9 months HR 2.13 [1.18–3.88], p < 0.05). Similarly, in the second or successive lines, mCRPC with NED showed worse PFS (4.0 vs. 7.5 months HR 2.43 [1.45–4.05] p < 0.05), DCR, PSA response and OS (12.53 vs. 18.03 months HR 1.86 [1.12–3.10] p < 0.05). The adverse impact of NED on PFS was consistence across all subgroups; we also noted a trend of worse PFS in patients with high vs. low NED. Conclusions: In our study, mCRPC with NED treated with Enzalutamide or Abiraterone showed worse clinical outcomes. NED assessment should be considered to optimize treatment decisions in the mCRPC setting. Full article

(This article belongs to the Special Issue Cell Biology: State-of-the-Art and Perspectives in Italy 2024)

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13 pages, 2299 KiB

Open AccessArticle

Immune Control of Human Cytomegalovirus (HCMV) Infection in HCMV-Seropositive Solid Organ Transplant Recipients: The Predictive Role of Different Immunological Assays

by Federica Zavaglio, Irene Cassaniti, Piera d’Angelo, Paola Zelini, Giuditta Comolli, Marilena Gregorini, Teresa Rampino, Lucia Del Frate, Federica Meloni, Carlo Pellegrini, Massimo Abelli, Elena Ticozzelli, Daniele Lilleri and Fausto Baldanti

Cells 2024, 13(16), 1325; https://doi.org/10.3390/cells13161325 - 8 Aug 2024

Cited by 2 | Viewed by 1258

Abstract

Human cytomegalovirus (HCMV) infection remains a major complication for solid organ transplant recipients (SOTRs). The aim of this study was to evaluate the role of HCMV-specific T cell immunity measured at the time of the HCMV-DNA peak in predicting the spontaneous clearance of infection. The performance of cytokine flow cytometry using infected dendritic cells (CFC-iDC), infected cell lysate (CFC-iCL) and pp65 peptide pool (CFC-pp65 pool) as stimuli, as well as ELISPOT assays using infected cell lysate (ELISPOT-iCL) and the pp65 peptide pool (ELISPOT-pp65 pool), was analysed. Among the 40 SOTRs enrolled, 16 patients (40%) required antiviral treatment for an HCMV infection (Non-Controllers), while the others spontaneously cleared the infection (Controllers). At the HCMV-DNA peak, the number of HCMV-specific CD4⁺ T cells detected by the CFC-iDC, CFC-iCL and CFC-pp65 pool assays in Controllers was higher than that detected in Non-Controllers, while no difference was observed in terms of HCMV-specific CD8⁺ T cell response. The same trend was observed when the HCMV-specific T cell response was measured by ELISPOT-iCL and ELISPOT-pp65 pool. We observed that the CD4⁺ CFC-pp65 pool assay was the best predictor of self-resolving HCMV infection at the time of the HCVM-DNA peak. The CFC-pp65 pool assay is able to discriminate between CD4⁺ and CD8⁺ T cell responses and could be used in daily clinical practice. Full article

(This article belongs to the Special Issue Cell Biology: State-of-the-Art and Perspectives in Italy 2024)

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13 pages, 2715 KiB

Open AccessArticle

Cellular and Genomic Instability Induced by the Herbicide Glufosinate-Ammonium: An In Vitro and In Vivo Approach

by Alfredo Santovito, Mattia Lambertini, Dáša Schleicherová, Enrico Mirone and Alessandro Nota

Cells 2024, 13(11), 909; https://doi.org/10.3390/cells13110909 - 24 May 2024

Cited by 4 | Viewed by 1383

Abstract

Glufosinate-ammonium (GLA), an organophosphate herbicide, is released at high concentrations in the environment, leading to concerns over its potential genotoxic effects. However, few articles are available in the literature reporting the possible cellular and nuclear effects of this compound. We assessed, by in vitro and in vivo micronucleus assays, the genotoxicity of GLA on cultured human lymphocytes and Lymnaea stagnalis hemocytes at six concentrations: 0.010 (the established acceptable daily intake value), 0.020, 0.050, 0.100, 0.200, and 0.500 µg/mL. In human lymphocytes, our results reveal a significant and concentration-dependent increase in micronuclei frequency at concentrations from 0.100 to 0.500 μg/mL, while in L. stagnalis hemocytes, significant differences were found at 0.200 and 0.500 μg/mL. A significant reduction in the proliferation index was observed at all tested concentrations, with the only exception of 0.010 μg/mL, indicating that the exposure to GLA could lead to increased cytotoxic effects. In L. stagnalis, a significant reduction in laid eggs and body growth was also observed at all concentrations. In conclusion, we provided evidence of the genomic and cellular damage induced by GLA on both cultured human lymphocytes and a model organism’s hemocytes; in addition, we also demonstrated its effects on cell proliferation and reproductive health in L. stagnalis. Full article

(This article belongs to the Special Issue Cell Biology: State-of-the-Art and Perspectives in Italy 2024)

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Review

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12 pages, 851 KiB

Open AccessReview

The Intricate Relationship Between Pulmonary Fibrosis and Thrombotic Pathology: A Narrative Review

by Giovanni Cenerini, Davide Chimera, Marta Pagnini, Erica Bazzan, Maria Conti, Graziella Turato, Alessandro Celi and Tommaso Neri

Cells 2024, 13(24), 2099; https://doi.org/10.3390/cells13242099 - 18 Dec 2024

Viewed by 1213

Abstract

Idiopathic pulmonary fibrosis (IPF) is associated with a significantly increased risk of thrombotic events and mortality. This review explores the complex bidirectional relationship between pulmonary fibrosis and thrombosis, discussing epidemiological evidence, pathogenetic mechanisms, and therapeutic implications, with a particular focus on the emerging role of extracellular vesicles (EVs) as crucial mediators linking fibrosis and coagulation. Coagulation factors directly promote fibrosis, while fibrosis itself activates thrombotic pathways. Retrospective studies suggest the benefits of anticoagulants in IPF, but prospective trials have faced challenges. Novel anticoagulants, profibrinolytic therapies, and agents targeting protease-activated receptors (PARs) show promise in preclinical studies and early clinical trials. EVs have emerged as key players in the pathogenesis of interstitial lung diseases (ILDs), serving as vehicles for intercellular communication and contributing to both fibrosis and coagulation. EV-based approaches, such as EV modulation, engineered EVs as drug delivery vehicles, and mesenchymal stem cell-derived EVs, represent promising therapeutic strategies. Ongoing research should focus on optimizing risk–benefit profiles, identifying predictive biomarkers, evaluating combination strategies targeting thrombotic, fibrotic, and inflammatory pathways, and advancing the understanding of EVs in ILDs to develop targeted interventions. Full article

(This article belongs to the Special Issue Cell Biology: State-of-the-Art and Perspectives in Italy 2024)

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20 pages, 3058 KiB

Open AccessReview

Mast Cells and Basophils in Major Viral Diseases: What Are the Correlations with SARS-CoV-2, Influenza A Viruses, HIV, and Dengue?

by Luca Gammeri, Serena Sanfilippo, Clara Alessandrello, Sebastiano Gangemi and Paola Lucia Minciullo

Cells 2024, 13(24), 2044; https://doi.org/10.3390/cells13242044 - 11 Dec 2024

Cited by 1 | Viewed by 1575

Abstract

The SARS-CoV-2 pandemic has significantly impacted global health and has led the population and the scientific community to live in fear of a future pandemic. Based on viral infectious diseases, innate immunity cells such as mast cells and basophils play a fundamental role in the pathogenesis of viral diseases. Understanding these mechanisms could be essential to better study practical therapeutic approaches not only to COVID-19 but also to other viral infections widely spread worldwide, such as influenza A, HIV, and dengue. In this literature review, we want to study these concepts. Mast cells and basophils intervene as a bridge between innate and acquired immunity and seem to have a role in the damage mechanisms during infection and in the stimulation of humoral and cellular immunity. In some cases, these cells can act as reservoirs and favor the replication and spread of the virus in the body. Understanding these mechanisms can be useful not only in therapeutic but also in diagnostic and prognostic perspectives. The prospects of applying artificial intelligence and machine learning algorithms for the creation of very accurate diagnostic/prognostic tools are interesting. Full article

(This article belongs to the Special Issue Cell Biology: State-of-the-Art and Perspectives in Italy 2024)

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24 pages, 3616 KiB

Open AccessReview

Breath and Sputum Analyses in Asthmatic Patients: An Overview

by Piera Soccio, Carla Maria Irene Quarato, Pasquale Tondo, Donato Lacedonia, Anela Hoxhallari, Maria Pia Foschino Barbaro and Giulia Scioscia

Cells 2024, 13(16), 1355; https://doi.org/10.3390/cells13161355 - 14 Aug 2024

Cited by 1 | Viewed by 2641

Abstract

Recent advancements in asthma management include non-invasive methodologies such as sputum analysis, exhaled breath condensate (EBC), and fractional exhaled nitric oxide (FeNO). These techniques offer a means to assess airway inflammation, a critical feature of asthma, without invasive procedures. Sputum analysis provides detailed insights into airway inflammation patterns and cellular composition, guiding personalized treatment strategies. EBC collection, reflecting bronchoalveolar lining fluid composition, provides a non-invasive window into airway physiology. FeNO emerges as a pivotal biomarker, offering insights into eosinophilic airway inflammation and aiding in asthma diagnosis, treatment monitoring, and the prediction of exacerbation risks. Despite inherent limitations, each method offers valuable tools for a more comprehensive assessment of asthma. Combining these techniques with traditional methods like spirometry may lead to more personalized treatment plans and improved patient outcomes. Future research is crucial to refine protocols, validate biomarkers, and establish comprehensive guidelines in order to enhance asthma management with tailored therapeutic strategies and improved patient outcomes. Full article

(This article belongs to the Special Issue Cell Biology: State-of-the-Art and Perspectives in Italy 2024)

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