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Biology subjects

Bongiovanni, A.

Publications and source records attributed to Bongiovanni, A..

9 recordsLinked to original sources

Anti-oxidant and anti-inflammatory Effects of Aerosolised microalgal-derived extracellular vesicles in Bronchial Epithelial-Macrophage Co-cultures at the Air-Liquid Interface

AbstractInflammation and oxidative stress are key drivers in the pathogenesis of chronic lung diseases, including asthma, pulmonary fibrosis, and chronic obstructive pulmonary disease. Extracellular vesicles derived from the marine microalga Tetraselmis chuii, referred to as nanoalgosomes, have recently gained attention as natural nanocarriers that possess inherent antioxidant and anti-inflammatory properties. In this study, we investigated the biocompatibility and protective effects of aerosolized nanoalgosomes in a bronchial epithelial-macrophage co-culture model at the air-liquid interface. Co-cultures of CALU-3 epithelial cells and differentiated THP-1 macrophages were primed with aerosolised nanoalgosomes and subsequently exposed to either oxidative stress (tert-butyl hydroperoxide) or an inflammatory stimulus (lipopolysaccharide; LPS). Epithelial barrier integrity and cytotoxicity were evaluated using transepithelial electrical resistance and lactate dehydrogenase release assays, respectively, while intracellular reactive oxygen species levels and cytokine secretion were measured to assess antioxidant and immunomodulatory responses. Nanoalgosomes were non-cytotoxic, preserved epithelial barrier integrity, and significantly reduced oxidative stress. In addition, nanoalgosomes priming attenuated LPS-induced secretion of pro-inflammatory cytokines (IL-1{beta}, IL-6, IL-8, IL-18, TNF-) as well as the anti-inflammatory cytokine IL-10, suggesting a balanced immunomodulatory response. Overall, aerosolized nanoalgosomes maintained epithelial homeostasis and mitigated both oxidative and inflammatory stress, underscoring their potential as a safe, sustainable, and effective therapeutic strategy for chronic inflammatory lung diseases. Given their natural origin, excellent biocompatibility, and suitability for aerosol delivery, nanoalgosomes represent a promising class of inhalable biotherapeutics.

pharmacology and toxicology↗

Nanoalgosomes from Tetraselmis chuii: Microalgal Extracellular Vesicles for UV Protection, Anti-Aging, and Skin Depigmentation

The search for effective dermocosmetic treatments has recently been accompanied by the growing demand for ingredients that are both naturally derived and sustainable. In this context, microalgae have emerged as a promising biofactory, producing bioactive compounds for skin health, widely recognized for their antioxidant, anti-inflammatory, and anti-aging activities. To leverage these properties, besides the conventional use of microalgal mass or extracts, the isolation and application of their secretome, including the extracellular vesicles named "nanoalgosomes", emerged as a novel and increasingly studied approach. EVs are membranous nanoparticles released by all cells and naturally efficient in the transport of both endogenous and exogenous bioactive molecules. Their unique biological properties make them ideal candidates for therapeutic and cosmetic applications. Here, we propose nanoalgosomes, as a sustainable and effective solution for innovative dermocosmetic treatments. In this study we exemplify the use of the microalgae Tetraselmis chuii, an edible, green and renewable bio-source of extracellular vesicles. We demonstrated the nanoalgosomes skin-health promoting potential, by employing the human skin cells as model to evidence the nanoalgosome ability to protect the cells from ultraviolet B (UVB) radiation-related damages, by reducing both the oxidative stress, and senescence-associated phenotype in UVB-exposed skin cells. Furthermore, nanoalgosomes modulate melanogenesis in UVB-stimulated melanocytes by downregulating tyrosinase, significantly reducing melanin content, supporting their role as photoprotective and pigmentation-modulating agents. Altogether, our results provide a solid foundation for the development of nanoalgosome-based formulations in dermocosmetic applications aimed at UV protection, anti-aging, and depigmentation, supporting the transition toward natural and sustainable skincare solutions.

cell biology↗

A decision-making tool to navigate through Extracellular Vesicle research and product development

Due to their intercellular communication properties and their involvement in a wide range of biological processes, extracellular vesicles (EVs) are increasingly being studied and exploited for different applications. Nevertheless, their complex nature and heterogeneity, as well as the challenges related to their isolation, purification and characterization procedures, require cautious assessment of the quality and quantity parameters to monitor. This translates into a multitude of choices and putative solutions that lie in front of any EV researcher, in both research and translational environments, resembling a labyrinth with multiple paths to cross and, possibly, more than one exit. In this respect, decision-making tools might represent our modern Ariadnes string to follow not to get lost or distracted along the journey, to choose the shorter and best-fit-to-source EV application(s) and vice versa. Here, we present the implementation of a multi-criteria EV decision-making grid (EV-DMG) as a novel, customizable, efficient and easy-to-use tool to support responsible EV research and innovation. By identifying and weighting key assessment criteria for comparing distinct EV-based preparations and/or processes, our EV-DMG may assist any EV community member in making informed, transparent and reproducible decisions regarding the EV sources and/or samples to be managed, as well as the most suitable production and/or analytical pipelines to be adopted for targeting a defined aim or application.

cell biology↗

Functional enzymatic assays to predict the potency of extracellular vesicles

The application of extracellular vesicles (EVs) as therapeutics or nanocarriers in cell-free therapies necessitates meticulous evaluations of different features, including their identity, bioactivity, batch-to-batch reproducibility, and stability. Given the inherent heterogeneity in EV preparations, this assessment demands sensitive functional assays to provide key quality control metrics, complementing established methods to ensure that EV preparations meet the required functionality and quality standards. Here, we introduce the detectEV assay, an enzymatic-based approach for assessing EV luminal cargo bioactivity and membrane integrity. This method is fast, cost-effective, and quantifiable through enzymatic units. Utilizing microalgae-derived EVs, known as nanoalgosomes, as model systems, we optimized the assay parameters and validated its sensitivity and specificity in quantifying the enzymatic activity of esterases within the EV lumen while also evaluating EV membrane integrity. Compared to conventional methods that assess physicochemical features of EVs, our single-step analysis efficiently detects batch-to-batch variations by evaluating changes in luminal cargo bioactivity and integrity across various EV samples, including differences under distinct storage conditions and following diverse isolation and exogenous loading methods, all using small sample sizes. The detectEV assays application to various human-derived EV types demonstrated its versatility and potential universality. Additionally, the assay effectively predicted EV functionality, such as the antioxidant activity of different nanoalgosome batches. Our findings underscore the detectEV assays utility in comprehensive characterization of EV functionality and integrity, enhancing batch-to-batch reproducibility and facilitating their therapeutic applications. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=98 SRC="FIGDIR/small/563745v3_ufig1.gif" ALT="Figure 1"> View larger version (35K): org.highwire.dtl.DTLVardef@1b1c552org.highwire.dtl.DTLVardef@11a70eorg.highwire.dtl.DTLVardef@eec5b7org.highwire.dtl.DTLVardef@1f699dd_HPS_FORMAT_FIGEXP M_FIG C_FIG

cell biology↗

Tetraspanin CD81 promotes leukemia stem cell function and represents a new therapeutic vulnerability in acute myeloid leukemia

Despite important progress over the last decade, acute myeloid leukemia (AML) is still associated with poor clinical outcome. Novel potent therapies ideally effective against AML stem cells (LSC), a major driver of leukemia initiation and progression, are urgently needed. In particular, targeting common AML-associated antigens at the stem and progenitor cell level represents an attractive therapeutic strategy to achieve deep long-term remissions and is currently the subject of intensive research efforts. In this study, we identified the tetraspanin CD81, a cell surface antigen frequently expressed on AML cells including LSC, as a new determinant of relapse and poor prognosis. CD81 expression was higher in AML cells compared to normal bone marrow cells, and more markedly expressed at relapse. We further showed that modulation of CD81 expression using gain- and loss-of-function approaches affected leukemia aggressiveness, tumor burden, LSC-homing and - xenoengraftment as well as mouse survival. Finally, anti-hCD81 monoclonal antibody-treatment combined with standard chemotherapy in mice with pre-established AML not only reduced leukemia burden but also prolonged relapse-free and overall survival. Collectively, these results identified a new efficacious and safe pharmacological strategy for targeting LSC, opening up novel therapeutic avenues to improve AML outcome. Key pointsO_LICD81 expression in AML including LSC is a new determinant of aggressive disease and poor prognosis. C_LIO_LIAnti-hCD81 monoclonal antibody-treatment of AML xenografts reduced leukemia burden and improved survival rates. C_LI

cancer biology↗

Microalgae as a novel biofactory for biocompatible and bioactive extracellular vesicles

Nanoalgosomes are extracellular vesicles (EVs) released by microalgal cells that can mediate intercellular and cross-kingdom communication. In the present study, starting from the optimized nanoalgosome manufacturing from cultures of marine microalgae, we evaluated their innate biological properties in preclinical models. Our investigation of nanoalgosome biocompatibility included toxicological analyses, starting from studies on the invertebrate model organism Caenorhabditis elegans, proceeding to hematological and immunological evaluations in mice and immune-compatibility ex vivo. Nanoalgosome biodistribution was evaluated in mice with accurate space-time resolution, and in C. elegans at cellular and subcellular levels. Further examination highlighted the antioxidant and anti-inflammatory bioactivities of nanoalgosomes. This holistic approach to nanoalgosome functional characterization showcases that nanoalgosomes are innate effectors and potential drug delivery system for novel cosmetic formulations and EV-based therapies.

cell biology↗

Three-dimensional imaging of vascular development in the mouse epididymis: a prerequisite to better understand the post-testicular immune context of spermatozoa

Long considered an accessory tubule of the male reproductive system, the epididymis is proving to be a key determinant of male fertility. In addition to its secretory role in ensuring functional maturation and survival of spermatozoa, the epididymis has a complex immune function. Indeed, it must manage both peripheral tolerance to sperm antigens foreign to the immune system and the protection of spermatozoa as well as the organ itself against pathogens ascending the epididymal tubule. Although our knowledge of the immunobiology of this organ is beginning to accumulate at the molecular and cellular levels, the organization of blood and lymphatic networks of this tissue, important players in the immune response, remains largely unknown. In the present report, we have taken advantage of a VEGFR3:YFP transgenic mouse model. Using high-resolution three-dimensional (3D) imaging and organ clearing coupled with multiplex immunodetections of lymphatic (LYVE1, PDPN, PROX1) and/or blood (PLVAP/Meca32) markers, we provide for the first time a simultaneous deep 3D view of the lymphatic and blood epididymal vasculature in the mature adult mouse as well as during postnatal development. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=199 HEIGHT=200 SRC="FIGDIR/small/505406v1_ufig1.gif" ALT="Figure 1"> View larger version (56K): org.highwire.dtl.DTLVardef@307802org.highwire.dtl.DTLVardef@170c07org.highwire.dtl.DTLVardef@116b006org.highwire.dtl.DTLVardef@7e7f66_HPS_FORMAT_FIGEXP M_FIG Summary of the expansion of the conventional and hybrid lymphatic vasculature during postnatal development of the murine epididymis. C_FIG

developmental biology↗

Pharmacological tuning of microRNA in FAP-derived Extracellular Vesicles by HDAC inhibitors promotes regeneration and reduces fibrosis in dystrophic muscles.

Functional interactions between cellular components of the muscle stem cell (MuSC) niche regulate the regenerative ability of skeletal muscles in physiological and pathological conditions; however, the identity of the mediators of these interactions remains largely unknown. We show here that fibro-adipogenic progenitor (FAP)-derived Extracellular Vesicles (EVs) mediate microRNA transfer to MuSCs, and that exposure of dystrophic FAPs to HDAC inhibitors (HDACi) increases the intra-EV levels of a subset of microRNAs (miRs), which cooperatively target biological processes of therapeutic interest, including regeneration, fibrosis and inflammation. In particular, we found that increased levels of miR206 in EVs released from FAPs of muscles from Duchenne dystrophic patients or mice (mdx) exposed to HDACi were associated with enhanced regeneration and inhibition of fibrosis of dystrophic muscles. Consistently, EVs from HDACi-treated dystrophic FAPs could stimulated MuSC activation and expansion ex vivo, and promoted regeneration, while inhibiting fibrosis and inflammation of dystrophic muscles, upon intramuscular transplantation, in vivo. These data reveal a potential for pharmacological modulation of FAP-derived EVs content as novel strategy for focal therapeutic interventions in Duchenne Muscular Dystrophy (DMD) and possibly other muscular diseases. Brief SummaryExtracellular Vesicles from HDACi-treated dystrophic FAPs promote regeneration, while inhibiting fibrosis and inflammation of dystrophic muscles

cell biology↗

ESCRT-mediated lysosome repair precedes lysophagy and promotes cell survival

Although lysosomes perform a number of essential cellular functions, damaged lysosomes represent a potential hazard to the cell. Such lysosomes are therefore engulfed by autophagic membranes in the process known as lysophagy, which is initiated by recognition of luminal glycoprotein domains by cytosolic lectins such as Galectin-3. Here we show that, under various conditions that cause injury to the lysosome membrane, components of the endosomal sorting complex required for transport (ESCRT) machinery are recruited. This recruitment occurs before that of Galectin-3 and the lysophagy machinery. Subunits of the ESCRT-III complex show a particularly prominent recruitment, which depends on the ESCRT-I component TSG101 and the TSG101- and ESCRT-III-binding protein ALIX. Interference with ESCRT recruitment abolishes lysosome repair and causes otherwise reversible lysosome damage to become cell lethal. Vacuoles containing the intracellular pathogen Coxiella burnetii show reversible ESCRT recruitment, and interference with this recruitment reduces intravacuolar bacterial replication. We conclude that the cell is equipped with an endogenous mechanism for lysosome repair which protects against lysosomal damage-induced cell death but which also provides a potential advantage for intracellular pathogens.

cell biology↗