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Biology subjects

Bernardini, S.

Publications and source records attributed to Bernardini, S..

5 recordsLinked to original sources

Co-occurrence of Yersinia pestis and other zoonoses during European prehistory

The infection of humans by the causal agent of Plague, Yersinia pestis, has been attested as far back as 5,500 BP. Although the specific patho-mechanism and ultimate origin of the disease caused by these prehistoric genomes remains unclear, the bacterium spread through Europe, likely during the Late Neolithic to Bronze Age (LNBA). In this study, we analysed 9 genomic samples originating from 8 different human individuals dating to around 4950 cal BP from the site of Grotta della Spinosa, Tuscany, Italy. Metagenomic screening of these samples reveals one individual (GSP013) to be co-infected by Yersinia pestis, Erysipelothrix rhusiopathiae, and Hepatitis B virus (HBV). At least three further individuals from the site were infected with HBV, indicating its wider presence within the community. The phylogenetic placement of Y. pestis in GSP013 shows that this strain is closely related to the earliest LNBA Caucasus genomes of the bacterium, basal to later European diversity. This represents the earliest evidence of Y. pestis in the Italian peninsula (and Southern Europe more widely) to date, predating previously discovered genomes by at least 200 years. Furthermore, we retrieved 60 newly reported ancient genomes of Erysipelothrix rhusiopathiae and Erysipelothrix tonsillarum from animals and humans, dating back from 8,300 BP to 100 BP. Of these new genomes, 15 of which stem from individuals known to be infected by Y. pestis. This contributes to our understanding of Y. pestis transmission in prehistoric Europe and possible reservoirs, and offers insights into disease dynamics in communities during the 3rd millennium BCE.

evolutionary biology↗

3D bioprinting directly affects proteomic signature and myogenic maturation in muscle pericytes-derived human myo-substitute.

Skeletal muscle tissue engineering (SMTE) has recently emerged to address major clinical challenges such as volumetric muscle loss. Here, we report a rotary wet-spinning (RoWS) biofabrication technique for producing human myo-substitutes with biomimetic architectures and functions. We show how the proposed technique may be used to establish a well-tailored, anisotropic microenvironment that promotes exceptional myogenic differentiation of human skeletal muscle-derived pericytes (hPeri). Using high-resolution mass spectrometry-based proteomics with the integration of literature-derived signaling networks, we uncovered that i) 3D biomimetic matrix environment (PEG-Fibrinogen) confers a lower mitogenicity microenvironment compared to standard 2D cultures, favoring the formation of contractile-competent bundles of pericytes-derived myotubes in an anchoring-independent 3D state, and ii) the bioprinting method promotes an upregulation of muscle matrix structural protein besides increasing contractile machinery proteins with respect to 3D bulk cultures. Finally, in vivo investigations demonstrate that the 3D bioprinted myo-substitute is fully compatible with the host ablated muscular tissue, exhibiting myo-substitute engraftment and muscle regeneration in a mouse VML model. Overall, the results show that 3D bioprinting has a superior capability for controlling the myogenic differentiation process on a macroscale and, with future refining, may have the potential to be translated into clinical practice.

bioengineering↗

Pleiotropic effect of Lactoferrin in the prevention and treatment of COVID-19 infection: in vivo, in silico and in vitro preliminary evidences

Lactoferrin, a multifunctional cationic glycoprotein, secreted by exocrine glands and neutrophils, possesses an antiviral activity extendable to SARS-CoV-2. We performed in vitro assays proving lactoferrin antiviral activity through direct attachment to both virus and cell surface components. This activity varied according to concentration (100/500g/ml), multiplicity of infection (0.1/0.01) and cell type (Vero E6/Caco-2 cells). Interestingly, the in silico results strongly supported the hypothesis of a direct recognition between the lactoferrin and the Spike S glycoprotein, thus hindering the viral entry into the cells. Hence, we conducted a clinical trial to investigate effect and tolerability of a liposomal lactoferrin formulation as a supplementary nutraceutical agent in mild-to-moderate and asymptomatic COVID-19 patients. A total of 92 mild-to-moderate (67/92) and asymptomatic (25/92) COVID-19 patients were recruited and divided in 3 groups according to the administered regimen. Thirty-two patients, 14 hospitalised and 18 in home-based insolation received oral and intranasal liposomal bovine lactoferrin (bLf), 32 hospitalised patients were treated with standard of care treatment (hydroxychloroquine, azitromicin and lopinavir/darunavir), and 28, in home-based isolation, did not take any medication. Furthermore, 32 COVID-19 negative, not-treated, healthy subjects were added as a control group for ancillary analysis. bLf-supplemented COVID-19 patients obtained an earlier and significant (p < 0,0001.) median rRT-PCR SARS-COV-2 RNA negative conversion than standard of care-treated and non-treated COVID-19 patients (14.25 vs 27.13 vs 32.61 days, respectively). In addition, bLf-supplemented COVID-19 patients showed significant fast clinical symptoms recovery than standard of care-treated and non-treated COVID-19 patients. Moreover, in bLf-supplemented patients, a significant decrease of either serum ferritin or IL-6 levels or host iron overload, all parameters characterizing inflammatory processes, were observed. Serum D-dimers was also found significantly decreased following bLf supplement. No adverse events were reported. These in vitro and in vivo observations led us to speculate a potential and safe supplementary role of Blf in the management of mild-to-moderate and asymptomatic COVID-19 patients.

microbiology↗

Biofabricating murine and human myo-substitutes for rapid volumetric muscle loss restoration

The importance of skeletal muscle tissue is undoubted being the controller of several vital functions including respiration and all voluntary locomotion activities. However, its regenerative capability is limited and significant tissue loss often leads to a chronic pathologic condition known as volumetric muscle loss. Here, we propose a biofabrication approach to rapidly restore skeletal muscle mass, 3D histoarchitecture and functionality. By recapitulating muscle anisotropic organization at the microscale level, we demonstrate to efficiently guide cell differentiation and myobundle formation both in vitro and in vivo. Of note, upon implantation, the biofabricated myo-substitutes support the formation of new blood vessels and neuromuscular junctions - pivotal aspects for cell survival and muscle contractile functionalities - together with an advanced along with muscle mass and force recovery. Together, these data represent a solid base for further testing the myo-substitutes in large animal size and a promising platform to be eventually translated into clinical scenarios.

bioengineering↗

Skeletal muscle-derived Human Mesenchymal Stem Cells: influence of different culture conditions on proliferative and myogenic capabilities

Skeletal muscle tissue is characterized by restrained self-regenerative capabilities, being ineffective in relation to trauma extension both in time span (e.g. chronic diseases) and in size (e.g. large trauma). For these reasons, tissue engineering and/or cellular therapies represent a valuable solution in the cases where the physiological healing process failed. Satellite cells, the putative skeletal muscle stem cells, have been the first solution explored to remedy the insufficient self-regeneration capacity. Nevertheless, some limitation related to donor age, muscle condition, expansion hitch and myogenic potentiality maintenance have limited their use as therapeutic tool. To overcome this hindrance, different stem cells population with myogenic capabilities have been investigated to evaluate their real potentiality for therapeutic approaches, but, as of today, the perfect cell candidate has not been identified yet. In this work, we analyze the characteristics of skeletal muscle-derived human Mesenchymal Stem Cells (hMSCs), showing the maintenance/increment of myogenic activity upon differential culture conditions. In particular, we investigate the influence of a commercial enriched growth medium (Cyto-Grow), and of a medium enriched with either human-derived serum (H.S.) or Platelet-rich Plasma (PrP), in order to set up a culture protocol useful for employing this cell population in clinical therapeutic strategies. The presented results reveal the remarkable effects of H.S. in the enhancement of hMSC proliferation and myogenic differentiation.

cell biology↗