1,720,985 research outputs found
Immunogenicity of two recombinant DNA COVID-19 vaccines in young and aged mice
Full text linkBackground: SARS-CoV-2 emerged in December 2019 and spread rapidly around
the world. Vaccination is the most effective way to control the pandemic morbidity
and mortality. While most of the currently available vaccines against COVID-19 have
shown high efficacy against the original strain of SARS-CoV-2, their effectiveness
has declined due to the emergence of new variants and diminished immunity remains
a major threat, especially in older individuals. Therefore, the development of safe and
effective vaccines that can be rapidly adapted to new SARS-CoV-2 variants represents
an urgent health priority. We assessed the immunogenicity of two DNA vaccines
against SARS-CoV-2 variants: pVAX-S1-TM-D614G and pVAX-S1-TM-INDUK.
Methods: pVAX-S1-TM-D614G, encoding the S1 spike subunit in fusion with the
transmembrane region, that allows protein trimerization as predicted by in silico
analysis, was constructed by recombinant DNA technologies; the dominant D614G
substitution was introduced by a PCR-based mutagenesis protocol. pVAX-S1-TM-
INDUK was obtained by the insertion of additional key mutations from Delta (E484Q
and L452R) and Alpha (N501Y and A570D) variants. Antigen expression was verified
in vitro by immunofluorescence assay. To test the immunogenicity of pVAX-S1-TM-
D614G and pVAX-S1-TM-INDUK, they were administered, via intramuscular
injection followed by electroporation, in young and aged mice. The elicited immune
responses were monitored for 6 months.
Results: pVAX-S1-TM-D614G and pVAX-S1-TM-INDUK were first validated in
vitro: a robust expression and membrane localization of antigenic proteins was
demonstrated on transiently transfected HEK-293 cells. Our candidates DNA vaccines
were then tested in vivo in both young (11 weeks of age) and aged (20 months of age)
C57BL/6 mice. When delivered by electroporation, they were able to trigger a
significant anti-SARS-CoV-2 antibody production in immunized mice, although
antibody titer declined 6 months after the second dose, especially in aged animals. Of note, a third booster dose, given at 6 months from the last vaccination, significantly
increased the magnitude of humoral immunity, suggesting that immune recall can
improve antibody durability. Moreover, we optimized a lipid nanoparticle formulation,
we called LNP15, to encapsulate DNA plasmids by microfluidic technology.
Preliminary in vitro and in vivo results obtained with a prototype DNA vaccine,
indicate that LNP15 can successfully encapsulate DNA vaccines for their easier
administration.
Conclusions: We developed two recombinant DNA vaccines (pVAX-S1-TM-D614G
and pVAX-S1-TM-INDUK) against SARS-CoV-2 variants, able to elicit a significant
anti-Spike antibody response in both young and aged mice. Although the humoral
response declined within 6 months, a booster dose can efficiently recall immune
memory and reverse anti-SARS-CoV-2 antibody waning even in aged population.
Moreover, LNP15 formulation might permit to successfully deliver candidate DNA
vaccines by intramuscular injection without electroporation. Given that DNA vaccines
can be easily adapted in response to new variants, are cheaper and more stable than
currently approved vaccines, they represent a promising strategy to achieve global
immunization
Biomaterial-Driven 3D Scaffolds for Immune Cell Expansion toward Personalized Immunotherapy
Full text linkImmunotherapy has emerged as a transformative medical approach in recent years, providing novel treatments for cancer eradication, autoimmune disorders, and infectious diseases. Fundamental to the success of therapy is the enrichment of the immune cell population, particularly T cells, natural killer cells, and dendritic cells. However, achieving a robust and long-term proliferation of immune cells is still challenging both in vivo and ex vivo. In vivo expansion leverages the patient's natural microenvironment and regulatory mechanisms through therapeutic interventions like immune checkpoint inhibitors, cytokine therapy, and targeted antibodies. This approach fosters long-term immune memory and sustained protection. In contrast, ex vivo expansion involves isolation, manipulation, and expansion of the immune cells under controlled conditions before reinfusion, allowing for precise control over the process and generating potent immune cell populations. Hydrogels, due to their tunable biomechanical properties, high biocompatibility, and ability to mimic the extracellular matrix, provide an ideal platform for both in vivo and ex vivo immune cell expansion. For instance, hydrogel-based scaffolds or beads can facilitate a controlled and efficient expansion of immune cells ex vivo, whereas injectable and implantable hydrogels can provide innovative solutions for enhancing immune cell activity within the patient supporting prolonged immune cell activity. This review aims to elucidate the importance of hydrogel-based strategies in immune cell expansion, advancing the development of effective, personalized immunotherapies to improve patient outcomes. STATEMENT OF SIGNIFICANCE: This review highlights the transformative potential of hydrogel-based 3D scaffolds in advancing personalized immunotherapy. By integrating in vivo and ex vivo strategies, hydrogels provide an innovative platform to enhance immune cell expansion, addressing critical challenges in immunotherapy. The discussion emphasizes the unique biomechanical and biochemical tunability of hydrogels, enabling precise mimicry of the extracellular matrix to support T cell proliferation, activation, and memory formation. These advances offer scalable, cost-effective solutions for producing high-quality immune cells, contributing to more effective cancer treatments, autoimmune disease management, and infectious disease control. By bridging materials science and immunology, this work underscores the pivotal role of hydrogels in shaping the future of immune-based therapies
Insights into the effect of polyethylene terephthalate (PET) microplastics on HER2 signaling pathways
Full text link: Plastic pollution poses a significant threat to both ecosystems and human health, as fragments of microscale size are daily inhaled and ingested. Such tiny specks are defined as microplastics (MPs), and although their presence as environmental contaminants is ubiquitous in the world, their possible effects at biological and physiological levels are still not clear. To explore the potential impacts of MP exposure, we produced and characterized polyethylene terephthalate (PET) micro-fragments, then administered them to living cells. PET is widely employed in the production of plastic bottles, and thus represents a potential source of environmental MPs. However, its potential effects on public health are hardly investigated, as the current bio-medical research on MPs mainly utilizes different models, such as polystyrene particles. This study employed cell viability assays and Western blot analysis to demonstrate cell-dependent and dose-dependent cytotoxic effects of PET MPs, as well as a significant impact on HER-2-driven signaling pathways. Our findings provide insight into the biological effects of MP exposure, particularly for a widely used but poorly investigated material such as PET
Plant-derived extracellular vesicles release combined with systemic DOX exhibits synergistic effects in 3D bioprinted triple-negative breast cancer
Full text linkTriple-negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer, lacking targeted therapeutic options. Hydrogels, particularly gelatin methacrylate (GelMA), have emerged as promising materials for localized drug delivery due to their biocompatibility and tunable properties. This study investigates a dual-delivery system for enhancing the treatment efficacy of triple-negative breast cancer (TNBC) using a combination of extracellular vesicles (EVs) derived from Citrus limon L. and the chemotherapeutic drug doxorubicin (DOX). We fabricated 3D bioprinted GelMA scaffolds to achieve localized and controlled release of EVs and evaluated their synergistic effects with systemic DOX delivery on both primary and metastatic 3D TNBC models. The GelMA scaffolds, especially those with 95 % methacrylation, exhibited higher stiffness, which enhanced their sustained release. Following 48-h incubation, the combination of EVs and DOX significantly increased cytotoxicity in the primary 3D TNBC model, reducing cell viability to approximately 30 % compared to controls. This was notably more effective than treatments with DOX or EVs alone. During the extended 7-day incubation period, the combination treatment continued to show superior efficacy, with persistently high levels of ROS generation and further reduction in cell viability. In a metastatic 3D TNBC model, a significant sensitivity to the combined treatment was observed, which notably inhibited aggregate formation and migration. Importantly, EVs-embedded scaffolds promoted the proliferation of human fibroblasts, highlighting their non-toxic nature, while concurrently inhibiting TNBC cell growth. This approach provides a promising strategy to improve the treatment outcomes of TNBC by exploiting the synergistic effects of local EVs release and systemic chemotherapy
Highly fusogenic multicomponent lipid nanoparticles for nucleic acid delivery and process for the preparation thereof
No full textLa presente invenzione è relativa al processo di preparazione di nanoparticelle
lipidiche (LNP) multicomponenti ad elevata fusogenicità cellulare per la
veicolazione di acidi nucleici e in particolare per la vaccinazione a DNA.
5 L’invenzione è anche relativa alle nanoparticelle così ottenute. In particolare, le
nanoparticelle lipidiche dell’invenzione sono ottenute combinando lipidi cationici e
lipidi ionizzabili in un rapporto specifico tra loro per essere somministrate sia
sottocute (via intradermica o intramuscolo) e sia per via sistemica con minori effetti
collaterali rispetto alle nanoparticelle lipidiche note nell’arte
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Impact of different 2D materials on the efficacy of photothermal and photodynamic therapy in 3D-bioprinted breast cancer
No full textThe convergence of nanotechnology and tissue engineering has paved the way for innovative cancer treatments that leverage the unique light absorption properties of nanomaterials. Indeed, photothermal therapy (PTT) and photodynamic therapy (PDT) utilize nanomaterials to convert near-infrared light into therapeutic energy for cancer treatment. This study focuses on the application of poly(lactic-co-glycolic acid) (PLGA) scaffolds, enhanced by graphene oxide, Ti3C2Tx MXene, and TiS2 transition metal dichalcogenides for PDT and PTT treatments evaluated within 3D-bioprinted breast cancers. Our scaffolds were designed to exploit the photothermal conversion efficiency and capability to generate reactive oxygen species (ROS) to compare the specific features of each 2D material. We demonstrated a reduction in tumor viability under scaffold irradiation, along with the exploration of biological responses to damage such as autophagy and pyroptosis, verifying that these scaffolds can differentially induce these processes depending on the light responsiveness of each material. The integration of these materials within 3D-printed scaffolds does not only enhance the therapeutic efficacy of PTT and PDT, but also offers a precise method to control the cellular environment after therapy, i.e. tissue regeneration and antibacterial effects, providing insights into the potential for these technologies to be adapted for personalized medicine for breast cancer treatment and reconstruction
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
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