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The umbilical cord blood (UCB) donated in public UCB banks is a source of hematopoietic stem cells (HSC) alternative to bone marrow for allogeneic HSC transplantation (HSCT). However, the high rejection rate of the donated units due to the strict acceptance criteria and the wide application of the haploidentical HSCT have resulted in significant limitation of the use of UCB and difficulties in the economic sustainability of the public UCB banks. There is an ongoing effort within the UCB community to optimize the use of UCB in the field of HSCT and a parallel interest in exploring the use of UCB for applications beyond HSCT i.e., in the fields of cell therapy, regenerative medicine and specialized transfusion medicine. In this report, we describe the mode of operation of the three public UCB banks in Greece as an example of an orchestrated effort to develop a viable UCB banking system by (a) prioritizing the enrichment of the national inventory by high-quality UCB units from populations with rare human leukocyte antigens (HLA), and (b) deploying novel sustainable applications of UCB beyond HSCT, through national and international collaborations. The Greek paradigm of the public UCB network may become an example for countries, particularly with high HLA heterogeneity, with public UCB banks facing sustainability difficulties and adds value to the international efforts aiming to sustainably expand the public UCB banking system. [ABSTRACT FROM AUTHOR]

Simple Summary: Adoptive immunotherapy has emerged as an effective alternative of mounting impact to the current standard of care in cancer, viral infections, and recently, autoimmunity. Key players in maintaining immune homeostasis are the regulatory T cells (Tregs), a major immunosuppressive cell subset and, therefore, an attractive candidate for the cellular therapy of autoimmune disorders or allo-responses in the transplantation setting. Notwithstanding the safety and tolerability of Tregs in early trials, their efficacy remains rather ill-defined, being limited by poor persistence and a lack of specificity, thus hindering widespread clinical application. However, the better biological understanding of in vivo Treg performance and the recent advances in genetic engineering have led to the next-generation Treg immunotherapy era, enabling the introduction of new features in Tregs and generating more potent and targeted Treg cellular therapies. In this review, we discuss the current achievements and existing challenges towards clinically translating Tregs into a living drug therapy for a variety of inflammatory conditions. Regulatory T cells (Tregs) are fundamental to maintaining immune homeostasis by inhibiting immune responses to self-antigens and preventing the excessive activation of the immune system. Their functions extend beyond immune surveillance and subpopulations of tissue-resident Treg cells can also facilitate tissue repair and homeostasis. The unique ability to regulate aberrant immune responses has generated the concept of harnessing Tregs as a new cellular immunotherapy approach for reshaping undesired immune reactions in autoimmune diseases and allo-responses in transplantation to ultimately re-establish tolerance. However, a number of issues limit the broad clinical applicability of Treg adoptive immunotherapy, including the lack of antigen specificity, heterogeneity within the Treg population, poor persistence, functional Treg impairment in disease states, and in vivo plasticity that results in the loss of suppressive function. Although the early-phase clinical trials of Treg cell therapy have shown the feasibility and tolerability of the approach in several conditions, its efficacy has remained questionable. Leveraging the smart tools and platforms that have been successfully developed for primary T cell engineering in cancer, the field has now shifted towards "next-generation" adoptive Treg immunotherapy, where genetically modified Treg products with improved characteristics are being generated, as regards antigen specificity, function, persistence, and immunogenicity. Here, we review the state of the art on Treg adoptive immunotherapy and progress beyond it, while critically evaluating the hurdles and opportunities towards the materialization of Tregs as a living drug therapy for various inflammation states and the broad clinical translation of Treg therapeutics. [ABSTRACT FROM AUTHOR]

Trade and colonization caused an unprecedented increase in Mediterranean human mobility in the first millennium BCE. Often seen as a dividing force, warfare is in fact another catalyst of culture contact. We provide insight into the demographic dynamics of ancient warfare by reporting genome-wide data from fifth-century soldiers who fought for the army of the Greek Sicilian colony of Himera, along with representatives of the civilian population, nearby indigenous settlements, and 96 present-day individuals from Italy and Greece. Unlike the rest of the sample, many soldiers had ancestral origins in northern Europe, the Steppe, and the Caucasus. Integrating genetic, archaeological, isotopic, and historical data, these results illustrate the significant role mercenaries played in ancient Greek armies and highlight how participation in war contributed to continental-scale human mobility in the Classical world.

There is an unmet need of models for early prediction of morbidity and mortality of Coronavirus disease-19 (COVID-19). We aimed to a) identify complement-related genetic variants associated with the clinical outcomes of ICU hospitalization and death, b) develop an artificial neural network (ANN) predicting these outcomes and c) validate whether complement-related variants are associated with an impaired complement phenotype. We prospectively recruited consecutive adult patients of Caucasian origin, hospitalized due to COVID-19. Through targeted next-generation sequencing, we identified variants in complement factor H/CFH, CFB, CFH-related, CFD, CD55, C3, C5, CFI, CD46, thrombomodulin/THBD, and A Disintegrin and Metalloproteinase with Thrombospondin motifs (ADAMTS13). Among 381 variants in 133 patients, we identified 5 critical variants associated with severe COVID-19: rs2547438 (C3), rs2250656 (C3), rs1042580 (THBD), rs800292 (CFH) and rs414628 (CFHR1). Using age, gender and presence or absence of each variant, we developed an ANN predicting morbidity and mortality in 89.47% of the examined population. Furthermore, THBD and C3a levels were significantly increased in severe COVID-19 patients and those harbouring relevant variants. Thus, we reveal for the first time an ANN accurately predicting ICU hospitalization and death in COVID-19 patients, based on genetic variants in complement genes, age and gender. Importantly, we confirm that genetic dysregulation is associated with impaired complement phenotype., (© 2022 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Plant growth promoting rhizobacteria (PGPR) are able to provide cross-protection against multiple stress factors and facilitate growth of their plant symbionts in many ways. The aim of this study was to isolate and characterize rhizobacterial strains under natural conditions, associated with naturally occurring representatives of wild plant species and a local tomato cultivar, growing in differently stressed Mediterranean ecosystems. A total of 85 morphologically different rhizospheric strains were isolated; twenty-five exhibited multiple in vitro PGP-associated traits, including phosphate solubilization, indole-3-acetic acid production, and 1-aminocyclopropane-1-carboxylate deaminase activity. Whole genome analysis was applied to eight selected strains for their PGP potential and assigned seven strains to Gammaproteobacteria, and one to Bacteroidetes. The genomes harboured numerous genes involved in plant growth promotion and stress regulation. They also support the notion that the presence of gene clusters with potential PGP functions is affirmative but not necessary for a strain to promote plant growth under abiotic stress conditions. The selected strains were further tested for their ability to stimulate growth under stress. This initial screening led to the identification of some strains as potential PGPR for increasing crop production in a sustainable manner.

Background/aims: Factor V Leiden heterozygosity occurs in 3-8% of the general European and US populations. Activated protein C resistance (APC-R)--a non-molecular laboratory test--can efficiently demonstrate the presence of this mutation and can be performed on most coagulation analyzers. On the other hand, fistula or graft thrombosis is a common and costly complication in hemodialysis patients. Our aim was to establish the value of APC-R determination in hemodialysis patients by assessing the risk of access thrombosis in patients with increased APC-R., Methods: A total of 133 patients (81 men, mean age 64.5 ± 14.9 years and 52 women, mean age 63.6 ± 15 years) were selected. Participants were divided into 2 groups: those with access thrombosis (54 patients, 40.6%) and those with no access thrombosis (79 patients, 59.4%), and they were tested for the most common congenital or acquired thrombophilia risk factors., Results: Overall, 12 patients (9%) had an increased APC-R and 10 of them had at least 1 episode of access thrombosis (83.3%). Univariate analysis to estimate crude odds ratio (OR) showed an OR of 8.8 (95% CI 1.8-41.8) times higher risk for access thrombosis in these patients. No significant differences were found after adjusting for age, hypertension, diabetes mellitus, coronary artery disease, cerebrovascular disease, peripheral arterial disease and malignancy. Sex was also a factor influencing thrombosis, presenting a higher OR for women (OR 2.2, 95% CI 1.1-4.4)., Conclusion: This study revealed a significant association between access thrombosis and increased APC-R in hemodialysis patients. This indicates that the determination of APC-R should be considered--especially, in populations with a high prevalence of Factor V Leiden--as proper anticoagulant therapy in these patients may reduce the risk of access thrombosis., (© 2015 S. Karger AG, Basel.)