Dendritic cells (DCs) hold promise for anti-cancer immunotherapy. However, clinically, their efficiency is limited and novel strategies to improve DC-mediated anti-tumor responses are needed. Human DCs display high content of sialic acids, which inhibits their maturation and co-stimulation capacity. Here, we aimed to understand whether exogenous desialylation of DCs improves their anti-tumor immunity. Compared to fully sialylated DCs, desialylated human DCs loaded with tumor-antigens showed enhanced ability to induce autologous T cells to proliferate, to secrete Th1 cytokines, and to specifically induce tumor cell apoptosis. Desialylated DCs showed an increased expression of MHC-I and -II, co-stimulatory molecules and an augmented secretion of IL-12. Desialylated HLA-A*02:01 DCs pulsed with gp100 peptides displayed enhanced peptide presentation through MHC-I, resulting in higher activation ofgp100280–288 specific CD8+ cytotoxic T cells. Desialylated murine DCs also exhibited increased MHC and co-stimulatory molecules and higher antigen cross-presentation via MHC-I. These DCs showed higher ability to activate antigen-specific CD4+ and CD8+ T cells, and to specifically induce tumor cell apoptosis. Collectively, our data demonstrates that desialylation improves DCs’ ability to elicit T cell-mediated anti-tumor activity, due to increased MHC-I expression and higher antigen presentation via MHC-I. Sialidase treatment of DCs may represent a technology to improve the efficacy of antigen loaded-DC-based vaccines for anti-cancer immunotherapy.

Biofilms are generally defined as communities of cells involved in a self-produced extracellular matrix adhered to a surface. In biofilms, the bacteria are less sensitive to host defense mechanisms and antimicrobial agents, due to multiple strategies, that involve modulation of gene expression, controlled metabolic rate, intercellular communication, composition, and 3D architecture of the extracellular matrix. These factors play a key role in streptococci pathogenesis, contributing to therapy failure and promoting persistent infections. The species of the pyogenic group together with Streptococcus pneumoniae are the major pathogens belonging the genus Streptococcus, and its biofilm growth has been investigated, but insights in the genetic origin of biofilm formation are limited. This review summarizes pyogenic streptococci biofilms with details on constitution, formation, and virulence factors associated with formation.

Surface modification of zinc oxide nanoparticles (ZnO NPs) is a strategy to tune their biocompatibility. Herein we report on the synthesis of a series of fluorescent ZnO NPs modified with 2-10% (3-glycidyloxypropyl)trimethoxysilane (GPTMS) to investigate the fluorescence properties and to explore their applications in microbiology and biomedicine. The obtained ZnO NPs were characterized by X-ray diffraction (XRD), high resolution transmission electron microscopy (HRTEM) and Fourier transform infrared spectroscopy (FTIR). Size reduction occurred from ca. 13 nm in unmodified ZnO to 3-4 nm in silane-modified samples and fluorescence spectra showed size-dependent variation of the photoemission bands' intensity. The antibacterial and cytotoxic activities were investigated on Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus aureus) bacteria, and in ovarian (A2780) and prostate (PC3) cancer cells by tetrazolium/formazan-based methods. The antibacterial effect was higher for E. coli than S. aureus, while the cytotoxic activity was similar for both cancer cells and varied with the particle size. Cell death by apoptosis, and/or necrosis versus autophagy, were explored by flow cytometry using an Annexin V based-method and transmission electron microscopy (TEM). The main mechanism of ZnO NPs toxicity may involve the generation of reactive oxygen species (ROS) and the induction of apoptosis or autophagy. This work revealed the potential utility of GPTMS-modified ZnO NPs in the treatment of bacterial infection and cancer.

Once released to the extracellular space, exosomes enable the transfer of proteins, lipids and RNA between different cells, being able to modulate the recipient cells' phenotypes. Members of the Rab small GTP-binding protein family, such as RAB27A, are responsible for the coordination of several steps in vesicle trafficking, including budding, mobility, docking and fusion. The use of gold nanoparticles (AuNPs) for gene silencing is considered a cutting-edge technology. Here, AuNPs were functionalized with thiolated oligonucleotides anti-RAB27A (AuNP@PEG@anti-RAB27A) for selective silencing of the gene with a consequent decrease of exosomes´ release by MCF-7 and MDA-MB-453 cells. Furthermore, communication between tumor and normal cells was observed both in terms of alterations in c-Myc gene expression and transportation of the AuNPs, mediating gene silencing in secondary cells.

Structural, spectroscopic and electrochemical properties of six complexes [AuCl(L1)](PF6)2.CH3CN (1), [AuCl(L2)](PF6)2 (2), [PtCl(L1)](BPh4).CH3CN (3), [PtCl(L2)](SO3CF3) (4), [CuCl2(L1)] (5) and [CuCl2(L2)].CH3CN (6) with modified 2,2':6',2''-terpyridine ligands, 4'-(4-methoxyphenyl)-2,2':6',2''-terpyridine (L1) and 4'-(4-methoxynaphthalen-1-yl)-2,2':6',2''-terpyridine (L2) were thoroughly investigated and a significant role of the substituent (4-methoxyphenyl or 4-methoxynaphthalen-1-yl) and the metal center was demonstrated. The naphthyl-based substituent was found to increase the emission quantum yield of the luminescent Au(iii) and Pt(ii) complexes. Furthermore, the antiproliferative potential of the reported complexes was examined towards human colorectal (HCT116) and ovarian (A2780) carcinoma cell lines as well as towards normal human fibroblasts. The Au(iii) complex 2 and Cu(ii) complex 5 were found to have a higher antiproliferative effect on HCT116 colorectal and A2780 ovarian carcinoma cells when compared with the Pt(ii) complex with the same ligand (4). The order of cytotoxicity in both cell lines is 2 > 6 > 1 > 3 > 4. Complex 2 seems to be more cytotoxic towards HCT116 and A2780 cancer cell lines with IC50 values 300x and 130x higher in normal human fibroblasts compared to the respective cancer cells. The viability loss induced by the complexes agrees with Hoechst 33258 staining and the typical morphological apoptotic characteristics like chromatin condensation and nuclear fragmentation and flow cytometry assay. The induction of apoptosis correlates with the induction of reactive oxygen species (ROS). Fluorescence microscopy analysis indicates that after 3 h of incubation, complexes 1-4 are localized inside HCT116 cells and the high levels of internalization correlate with their cytotoxicity.

Streptococcus dysgalactiae subsp. dysgalactiae (SDSD) is a major cause of bovine mastitis and has been regarded as an animal-restricted pathogen, although rare infections have been described in humans. Previous studies revealed the presence of virulence genes encoded by phages of the human pathogen Group A Streptococcus pyogenes (GAS) in SDSD isolated from the milk of bovine udder with mastitis. The isolates SDSD VSD5 and VSD13 could adhere and internalize human primary keratinocyte cells, suggesting a possible human infection potential of bovine isolates. In this work, the in vitro and in vivo potential of SDSD to internalize/adhere human cells of the respiratory track and zebrafish as biological models was evaluated. Our results showed that, in vitro, bovine SDSD strains could interact and internalize human respiratory cell lines and that this internalization was dependent on an active transport mechanism and that, in vivo, SDSD are able to cause invasive infections producing zebrafish morbidity and mortality. The infectious potential of these isolates showed to be isolate-specific and appeared to be independent of the presence or absence of GAS phage-encoded virulence genes. Although the infection ability of the bovine SDSD strains was not as strong as the human pathogenic S. pyogenes in the zebrafish model, results suggested that these SDSD isolates are able to interact with human cells and infect zebrafish, a vertebrate infectious model, emerging as pathogens with zoonotic capability.

The water-soluble 1D helical coordination polymer [Ag(Tpms)]n (1) [Tpms=tris(pyrazolyl)methane sulfonate, (-)O3SC(pz)3; pz=pyrazolyl] was synthesized and fully characterized, its single-crystal X-ray diffraction analysis revealing the ligand acting as a bridging chelate N3-donor ligand. The antiproliferative potential of 1 was performed on two human tumour cell lines, A2780 and HCT116, and in normal fibroblasts, with a much higher effect in the former cell line (IC50 of 0.04muM) as compared to the latter cell line and to normal fibroblasts. Compound 1 does not alter cell cycle progression but interferes with the adherence of A2780 cells triggering cell apoptosis. Apoptosis appears to occur via the extrinsic pathway (no changes in mitochondria membrane potential, reactive oxygen species (ROS) and pro-apoptotic (B-cell lymphoma 2 (BCL-2) associated protein (BAX))/anti-apoptotic (BCL-2) ratio) being this hypothesis also supported by the presence of silver mainly in the supernatants of A2780 cells. Results also indicated that cell death via autophagy was triggered. Proteomic analysis allowed us to confirm that compound 1 is able to induce a stress response in A2780 cells that is related with its antiproliferative activity and the trigger of apoptosis.

New hetero-arylidene-9(10H)-anthrone derivatives (1) were synthesized from reaction of 1,2-dimethyl-3-alkyl imidazolium salts (2) and 9-anthracenecarboxaldehyde. Ion exchange of the anion with dioctyl sulfosuccinate and lithium bis(trifluoromethanesulfonyl)imide led to the preparation of other derivatives. The antiproliferative effect of the compounds was evaluated in human ovarian (A2780) and colorectal (HCT116) carcinoma cell lines and in normal primary human fibroblasts. Compound 1 presented an antiproliferative effect related to the imidazolium pattern of substitution with compounds having a decyl group at the R-position (1c and 3c) showing the highest cytotoxic activities in all cell lines independently of the counter ion. Compounds 1b and 1c internalize A2780 cancer cells via a passive or an active transport, respectively, inducing A2780 cell death via an extrinsic apoptosis (1b) or intrinsic apoptosis and oncosis (1c). The localization of both compounds in the cytoplasm coupled to the absence of reactive oxygen species (ROS) induction suggest that the mechanisms of toxicity might be different than those of other anthracyclines currently used in chemotherapy.

A simple oxidative ring rearrangement of diversely substituted 1-(2-amminoaryl)-tetrahydro-β-carbolines has been developed to generate architecturally interesting tetrahydro-1H-indolo[2,3-b]pyrrolo[3,2-c]quinolones. This unique transformation involves four reaction centers (aniline, C1-carboline and C2/C3 of indole) and utilizes tert-butylhypochlorite as the reagent. The generic nature of the reaction was demonstrated by the synthesis of a wide variety of analogs 9a–j. A putative reaction mechanism was proposed. Cytotoxicity screening of these compounds against three human cancer cells (A2780 ovarian and HCT116 colorectal carcinoma cell lines and A549 lung adenocarcinoma cell line) revealed selective inhibition of proliferation of the A2780 human ovarian carcinoma cell line by one of the molecules 9a with an IC50 of 14 μM. No cytotoxic activity was observed in human normal fibroblasts for concentrations up to 100 μM. Compound 9a induced hyperpolarization of the mitochondrial membrane potential of the A2780 cell line leading to an increase of reactive oxygen species (ROS) that trigger cell death via apoptosis. Interestingly, compound 9a was also able to induce cell death via autophagy. Compounds that induce apoptosis and autophagy, thus leading to cancer cells’ death, are good candidates for cancer therapy.

Reactions between 4′-phenyl-terpyridine (L) and several Cu(II) salts (p-toluenesulfonate, benzoate and o-, m- or p-hydroxybenzoate) led to the formation of [Cu(p-SO3C6H4CH3)L(H2O)2](p-SO3C6H4CH3) (1), [Cu(OCOPh)2L] (2), [Cu(o-OCOC6H4OH)2L] (3), [Cu(m-OCOC6H4OH)2L]·MeOH (4·MeOH) and [Cu(p-OCOC6H4OH)2L]·2H2O (5·2H2O), which were characterized by elemental and TG-DTA analyses, ESI-MS, IR spectroscopy and single crystal X-ray diffraction, as well as by conductivimetry. In all structures the Cu atoms present N3O3 octahedral coordination geometries, which, in 2–5, are highly distorted as a result of the chelating-bidentate mode of one of the carboxylate ligands. Intermolecular π⋯π stacking interactions could also be found in 2–5 (in the 3.569–3.651 Å range and involving solely the pyridyl rings). Medium–strong hydrogen bond interactions lead to infinite 1D chains (in 1 and 4) and to an infinite 2D network (in 5). Compounds 1 and 4 show high in vitro cytotoxicity towards HCT116 colorectal carcinoma and HepG2 hepatocellular carcinoma cell lines. The antiproliferative potential of compound 1 is due to an increase of the apoptotic process that was confirmed by Hoechst staining, flow cytometry and RT-qPCR. All compounds able to non-covalently intercalate the DNA helix and induce in vitro pDNA double-strand breaks in the absence of H2O2. Concerning compound 1, the hydroxyl radical and singlet oxygen do not appear to be involved in the pDNA cleavage process and the fact that this cleavage also occurs in the absence of molecular oxygen points to a hydrolytic mechanism of cleavage.

A new and never before reported hetero-arylidene-9(10H)-anthrone structure (4) was unexpectedly isolated on reaction of 1,2-dimethyl-3-ethylimidazolium iodide (2) and 9-anthracenecarboxaldehyde (3) under basic conditions. Its structure was unequivocally confirmed by X-ray crystallography. No cytotoxicity in human healthy fibroblasts and in two different cancer cell lines was observed, indicating its applicability in biological systems. Compound 4 interacts with CT-DNA by intercalation between the adjacent base pairs of DNA with a high binding affinity [Kb = 2.0 (±0.20) × 105 m–1], which is 10 × higher than that described for doxorubicin [Kb = 3.2 (±0.23) × 104 m–1]. Furthermore, compound 4 quenches the fluorescence emission of a GelRed–CT-DNA system with a quenching constant (KSV) of 3.3 (±0.3) × 103 m–1 calculated by the Stern–Volmer equation.