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Microbiologically Influenced Corrosion (MIC) is one of the main threats for marine infrastructures, leading to severe safety and environmental risks associated with structural failures and/or leakages of dangerous fluids, together with potential huge economic losses and reputational damage for the involved parts. For a safe design and a proper installation of infrastructure systems in contact with the seabed, a deep knowledge of the site-specific microbial community of the sediments should be beneficial. Therefore, in addition to the simple detection or the sole quantification of Sulphate-Reducing Bacteria (SRB), the whole characterization of the microbial members involved in MIC phenomena is desirable. In this study, 16S rRNA-based comparison between bacterial communities thriving in offshore and nearshore marine sediments was performed, with a focus on the main bacterial groups putatively responsible for MIC. The nearshore sediments were significantly enriched in bacterial members associated with human and organic compounds contamination belonging to the Bacteroidota, Desulfobacterota, and Firmicutes phyla, while the offshore sediments hosted Alphaproteobacteria, Nitrospinota, and Nitrospirota members, representative of a low anthropogenic impact. Quantitative PCR targeting the dsrA gene and detailed community analyses revealed that the nearshore sediments were significantly enriched in SRB mainly affiliated to the Desulfobulbus and Desulfosarcina genera potentially involved in biocorrosion, compared to the offshore ones. These results suggest that the bacterial community associated with the high concentration of organic compounds derived by an elevated anthropogenic impact is likely to favour MIC. Such observations highlight the importance of microbiological investigations as prevention strategy against MIC processes, aiming both at characterizing sites for the establishment of new infrastructures and at monitoring those already installed. [ABSTRACT FROM AUTHOR]

This review focuses on the role of human red blood cells (RBCs) as drug carriers. First, a general introduction about RBC physiology is provided, followed by the presentation of several cases in which RBCs act as natural carriers of drugs. This is due to the presence of several binding sites within the same RBCs and is regulated by the diffusion of selected compounds through the RBC membrane and by the presence of influx and efflux transporters. The balance between the influx/efflux and the affinity for these binding sites will finally affect drug partitioning. Thereafter, a brief mention of the pharmacokinetic profile of drugs with such a partitioning is given. Finally, some examples in which these natural features of human RBCs can be further exploited to engineer RBCs by the encapsulation of drugs, metabolites, or target proteins are reported. For instance, metabolic pathways can be powered by increasing key metabolites (i.e., 2,3-bisphosphoglycerate) that affect oxygen release potentially useful in transfusion medicine. On the other hand, the RBC pre-loading of recombinant immunophilins permits increasing the binding and transport of immunosuppressive drugs. In conclusion, RBCs are natural carriers for different kinds of metabolites and several drugs. However, they can be opportunely further modified to optimize and improve their ability to perform as drug vehicles. [ABSTRACT FROM AUTHOR]

The gyrate atrophy of the choroid and retina (GACR) is a rare genetic disease for which no definitive cure is available. GACR is due to the deficit of ornithine aminotransferase (hOAT), a pyridoxal 5′-phosphate-dependent enzyme responsible for ornithine catabolism. The hallmark of the disease is plasmatic ornithine accumulation, which damages retinal epithelium leading to progressive vision loss and blindness within the fifth decade. Here, we characterized the biochemical properties of tetrameric and dimeric hOAT and evaluated hOAT loaded in red blood cells (RBCs) as a possible enzyme replacement therapy (ERT) for GACR. Our results show that (i) hOAT has a relatively wide specificity for amino acceptors, with pyruvate being the most suitable candidate for ornithine catabolism within RBCs; (ii) both the tetrameric and dimeric enzyme can be loaded in RBC retaining their activity; and (iii) hOAT displays reduced stability in plasma, but is partly protected from inactivation upon incubation in a mixture mimicking the intracellular erythrocyte environment. Preliminary ex vivo experiments indicate that hOAT-loaded RBCs are able to metabolize extracellular ornithine at a concentration mimicking that found in patients, both in buffer and, although with lower efficiency, in plasma. Overall, our data provide a proof of concept that an RBC-mediated ERT is feasible and can be exploited as a new therapeutic approach in GACR. [ABSTRACT FROM AUTHOR]

Radial nerve palsies present a challenging clinical scenario, often leading to substantial functional impairment. This study focuses on evaluating the outcomes of tendon transfer surgeries in patients with post-traumatic radial nerve injuries. The radial nerve, vital for upper limb movements, faces various etiologies, such as trauma, compression, or idiopathy. Patients with radial nerve palsy encounter difficulties in daily activities, emphasizing the need for effective management strategies. The research introduces a novel evaluation protocol, aiming to comprehensively assess tendon transfer outcomes. This protocol incorporates functional movements of wrist and finger joints, encompassing both objective and subjective parameters. The retrospective study includes eleven patients treated between 2010 and 2022, with a minimum follow-up of one year post-surgery. Tendon transfers demonstrated positive results. The evaluation protocol covers a wide range of parameters, including wrist and finger mobility, thumb function, grip strength, and patient satisfaction. The results indicate successful restoration of motor function, with an average grip strength of 70% compared to the healthy arm. The proposed evaluation protocol facilitates standardized and reproducible assessment, minimizing subjective errors in clinical evaluations. Despite the study's limitations, such as a relatively small sample size, the findings underscore the effectiveness of tendon transfers in treating radial nerve palsies. The introduced evaluation scheme provides a comprehensive and reproducible approach to assess outcomes, contributing to the global standardization of tendon transfer assessments in radial nerve injuries. [ABSTRACT FROM AUTHOR]

Background: In the Mediterranean basin, three Leishmania species have been identified: L. infantum, L. major and L. tropica, causing zoonotic visceral leishmaniasis (VL), zoonotic cutaneous leishmaniasis (CL) and anthroponotic CL, respectively. Despite animal models and genomic/transcriptomic studies provided important insights, the pathogenic determinants modulating the development of VL and CL are still poorly understood. This work aimed to identify host transcriptional signatures shared by cells infected with L. infantum, L. major, and L. tropica, as well as specific transcriptional signatures elicited by parasites causing VL (i.e., L. infantum) and parasites involved in CL (i.e., L. major, L. tropica). Methodology/Principal findings: U937 cells differentiated into macrophage-like cells were infected with L. infantum, L. major and L. tropica for 24h and 48h, and total RNA was extracted. RNA sequencing, performed on an Illumina NovaSeq 6000 platform, was used to evaluate the transcriptional signatures of infected cells with respect to non-infected cells at both time points. The EdgeR package was used to identify differentially expressed genes (fold change > 2 and FDR-adjusted p-values < 0.05). Then, functional enrichment analysis was employed to identify the enriched ontology terms in which these genes are involved. At 24h post-infection, a common signature of 463 dysregulated genes shared among all infection conditions was recognized, while at 48h post-infection the common signature was reduced to 120 genes. Aside from a common transcriptional response, we evidenced different upregulated functional pathways characterizing L. infantum-infected cells, such as VEGFA-VEGFR2 and NFE2L2-related pathways, indicating vascular remodeling and reduction of oxidative stress as potentially important factors for visceralization. Conclusions: The identification of pathways elicited by parasites causing VL or CL could lead to new therapeutic strategies for leishmaniasis, combining the canonical anti-leishmania compounds with host-directed therapy. Author summary: Leishmaniasis is a zoonosis caused by the intracellular parasite of the genus Leishmania. In the Mediterranean region, the human disease can be present mainly in two forms: cutaneous leishmaniasis (CL) and visceral leishmaniasis (VL), which can be fatal if untreated. The clinical presentation of the disease depends on the parasite species and host characteristics. However, the molecular mechanisms underlying the development of the visceral form of leishmaniasis are not yet fully understood. In this study, we have determined the gene expression profile in cells infected by three Leishmania species (L. infantum, L. major, L. tropica) responsible for different forms of the disease. The results have allowed us to identify an expression profile (and the related pathways) shared by cells infected by all Leishmania species. Aside this common response, we also identified a transcriptional response distinguishing cells infected by L. infantum, L. major or L. tropica, as well as the relevant pathways in which these genes participate. Therefore, our results contribute to the knowledge of the host cell mechanisms that are activated along infection with different Leishmania species causing different forms of the disease and, therefore, may help develop new host-directed therapy for Leishmaniasis. [ABSTRACT FROM AUTHOR]