Generation of Monocyte-Derived Dendritic Cells with Differing Sialylated Phenotypes.

Sialic acids are negatively charged monosaccharides typically found at the termini of cell surface glycans. Due to their hydrophilicity and biophysical characteristics, they are involved in numerous biological processes, such as modulation of the immune response, recognition of self and non-self antigens, carbohydrate-protein interactions, etc. The cellular content of sialic acid is regulated by sialidase, which catalyzes the removal of sialic acid residues. Several studies have shown that sialo-glycans are critical in monitoring immune surveillance by engaging with cis and trans inhibitory Siglec receptors on immune cells. Likewise, glyco-immune checkpoints in cancer are becoming crucial targets for developing immunotherapies. Additionally, dendritic cells (DCs) are envisioned as an important component in immunotherapies, especially in cancer research, due to their unique role as professional antigen-presenting cells (APC) and their capacity to trigger adaptive immune responses and generate immunologic memory. Nevertheless, the function of DCs is dependent on their full maturation. Immature DCs have an opposing function to mature DCs and a high sialic acid content, which further dampens their maturation level. This downregulates the ability of immature DCs to activate T-cells, leading to a compromised immune response. Consequently, removing sialic acid from the cell surface of human DCs induces their maturation, thus increasing the expression of MHC molecules and antigen presentation. In addition, it can restore the expression of co-stimulatory molecules and IL-12, resulting in DCs having a higher ability to polarize T-cells toward a Th1 phenotype and specifically activate cytotoxic T-cells to kill tumor cells. Therefore, sialic acid has emerged as a key modulator of DCs and is being used as a novel target to advance their therapeutic use. This study provides a unique approach to treat in vitro monocyte-derived DCs with sialidase, aimed at generating DC populations with different cell surface sialic acid phenotypes and tailored maturation and co-stimulatory profiles.

Computational Approaches Drive Developments in Immune-Oncology Therapies for PD-1/PD-L1 Immune Checkpoint Inhibitors.

Computational approaches in immune-oncology therapies focus on using data-driven methods to identify potential immune targets and develop novel drug candidates. In particular, the search for PD-1/PD-L1 immune checkpoint inhibitors (ICIs) has enlivened the field, leveraging the use of cheminformatics and bioinformatics tools to analyze large datasets of molecules, gene expression and protein-protein interactions. Up to now, there is still an unmet clinical need for improved ICIs and reliable predictive biomarkers. In this review, we highlight the computational methodologies applied to discovering and developing PD-1/PD-L1 ICIs for improved cancer immunotherapies with a greater focus in the last five years. The use of computer-aided drug design structure- and ligand-based virtual screening processes, molecular docking, homology modeling and molecular dynamics simulations methodologies essential for successful drug discovery campaigns focusing on antibodies, peptides or small-molecule ICIs are addressed. A list of recent databases and web tools used in the context of cancer and immunotherapy has been compilated and made available, namely regarding a general scope, cancer and immunology. In summary, computational approaches have become valuable tools for discovering and developing ICIs. Despite significant progress, there is still a need for improved ICIs and biomarkers, and recent databases and web tools have been compiled to aid in this pursuit.

Prevalence and risk factors of syphilis and human immunodeficiency virus co-infection at a university hospital in Brazil.

INTRODUCTION: The incidence of syphilis has increased since the 1970s. METHODS: This was a descriptive and analytical cross-sectional study with a non-probabilistic sample. RESULTS: Of 973 patients with human immunodeficiency virus, 179 (18.4%) tested positive for both human immunodeficiency virus and syphilis, 84.8% were men, 50.9% were aged between 36 and 50 years, 47.8% with syphilis were diagnosed with human immunodeficiency virus for 10-20 years, and 40.3% received antiretroviral therapy for 10-20 years. CONCLUSIONS: The prevalence of syphilis in patients with human immunodeficiency virus is higher than expected, making it urgent to adopt efficient public health measures.

Prevalence and risk factors of syphilis and human immunodeficiency virus co-infection at a university hospital in Brazil

Abstract INTRODUCTION The incidence of syphilis has increased since the 1970s. METHODS This was a descriptive and analytical cross-sectional study with a non-probabilistic sample. RESULTS: Of 973 patients with human immunodeficiency virus, 179 (18.4%) tested positive for both human immunodeficiency virus and syphilis, 84.8% were men, 50.9% were aged between 36 and 50 years, 47.8% with syphilis were diagnosed with human immunodeficiency virus for 10-20 years, and 40.3% received antiretroviral therapy for 10-20 years. CONCLUSIONS The prevalence of syphilis in patients with human immunodeficiency virus is higher than expected, making it urgent to adopt efficient public health measures.

Viral inactivation in hemotherapy: systematic review on inactivators with action on nucleic acids.

The aim of this study was to conduct a systematic review on the photoinactivators used in hemotherapy, with action on viral genomes. The SciELO, Science Direct, PubMed and Lilacs databases were searched for articles. The inclusion criterion was that these should be articles on inactivators with action on genetic material that had been published between 2000 and 2010. The key words used in identifying such articles were "hemovigilance", "viral inactivation", "photodynamics", "chemoprevention" and "transfusion safety". Twenty-four articles on viral photoinactivation were found with the main photoinactivators covered being: methylene blue, amotosalen HCl, S-303 frangible anchor linker effector (FRALE), riboflavin and inactin. The results showed that methylene blue has currently been studied least, because it diminishes coagulation factors and fibrinogen. Riboflavin has been studied most because it is a photoinactivator of endogenous origin and has few collateral effects. Amotosalen HCl is effective for platelets and is also used on plasma, but may cause changes both to plasma and to platelets, although these are not significant for hemostasis. S-303 FRALE may lead to neoantigens in erythrocytes and is less indicated for red-cell treatment; in such cases, PEN 110 is recommended. Thus, none of the methods for pathogen reduction is effective for all classes of agents and for all blood components, but despite the high cost, these photoinactivators may diminish the risk of blood-transmitted diseases.

Viral inactivation in hemotherapy: systematic review on inactivators with action on nucleic acids

The aim of this study was to conduct a systematic review on the photoinactivators used in hemotherapy, with action on viral genomes. The SciELO, Science Direct, PubMed and Lilacs databases were searched for articles. The inclusion criterion was that these should be articles on inactivators with action on genetic material that had been published between 2000 and 2010. The key words used in identifying such articles were "hemovigilance", "viral inactivation", "photodynamics", "chemoprevention" and "transfusion safety". Twenty-four articles on viral photoinactivation were found with the main photoinactivators covered being: methylene blue, amotosalen HCl, S-303 frangible anchor linker effector (FRALE), riboflavin and inactin. The results showed that methylene blue has currently been studied least, because it diminishes coagulation factors and fibrinogen. Riboflavin has been studied most because it is a photoinactivator of endogenous origin and has few collateral effects. Amotosalen HCl is effective for platelets and is also used on plasma, but may cause changes both to plasma and to platelets, although these are not significant for hemostasis. S-303 FRALE may lead to neoantigens in erythrocytes and is less indicated for red-cell treatment; in such cases, PEN 110 is recommended. Thus, none of the methods for pathogen reduction is effective for all classes of agents and for all blood components, but despite the high cost, these photoinactivators may diminish the risk of blood-transmitted diseases.

Characterisation and classification of phylloplane yeasts from Portugal related to the genus Taphrina and description of five novel Lalaria species.

Taphrina Fries is a genus of dimorphic ascomycetes comprising more than 90 species distinguished by the specific infections they produce on different vascular plants. Their filamentous states are restricted to parasitised plant tissue whereas the yeast states are saprobic and can be grown on artificial media. The latter coincide with the anamorphic phases and have been given separate nomenclatural status by the erection of the genus Lalaria R.T. Moore. In its original circumscription Lalaria included only 23 yeast states of known species of Taphrina and its creation was then redundant. Here we describe five novel species in the genus Lalaria to accommodate a total of 44 yeast isolates obtained mainly from leaf surfaces (phylloplane) of different plants in Portugal: Lalaria arrabidae sp. nov. (one strain), L. carpini sp. nov. (one strain), L. inositophila sp. nov. (37 strains), L. kurtzmanii sp. nov. (one strain) and L. veronaerambellii sp. nov. (four strains). L. inositophila was notable for its widespread occurrence since it was recovered during two consecutive years from the leaves of miscellaneous plant species. In the absence of sexual states and of unequivocal associations to particular host plants, the taxonomic relationship of the novel species to the yeast states of Taphrina available from culture collections was verified by the comparative analysis of physiological and molecular characteristics. The latter included PCR fingerprinting using single primers for microsatellite regions, sequencing of the 5' end of the 26S rRNA (LSU) gene (D1/D2 domains) and of the ITS1 and ITS2 rDNA spacer regions, and DNA-DNA hybridisation experiments. An emended description of the genus Lalaria is provided.