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Searching for new drugs is an expensive and time-consuming process, but it remains vital for the treatment of many old and new diseases. The availability of current advanced technologies has led to an acceleration of the drug discovery process, facilitating further development of personalized therapies. Sometimes, to obtain the desired therapeutic goals, the drug administration strategy can be of primary importance. Equally important, however, is the understanding of the complex mechanisms of action of new drugs on different cellular and molecular targets, both when the drugs are used alone and when they are administered in combination with other molecules.

Circulating mannose-binding lectin (MBL) plays an important role in the progression of tissue damage caused by ischemic events, an account of its high-affinity, multivalent binding to carbohydrate arrays exposed on damaged endothelium (damage-associated molecular patterns, DAMPS). MBL inhibitors have therefore been proposed as a novel protective therapeutic strategy to prevent secondary injury. We developed a new, convenient, robust surface plasmon resonance (SPR) assay for in vitro screening of compounds interfering with the binding of native human MBL to an appropriate chip surface functionalized with a pattern of sugar moieties mimicking DAMPS. We also characterized the procedure to regenerate the chip surface after each experimental session, accomplished by sequential cleaning with piranha solution followed by UV exposure. The SPR assay detects the specific binding of human recombinant MBL and native MBL present in human serum, and can identify inhibitors of this binding. We observed inhibitory effects of mannose (IC50 ≅ 5 mM), of a nine mannose residues carrying glycan (IC50 ≅ 0.33 mg/mL, corresponding to ~ 175 μM), and mainly mannose-coated gold nanoparticles (IC50 ≅ 1.1 μg /mL). These in vitro results serve as a basis for testing the protective properties of these molecules/nanoparticles later inthe more expensive and time-consuming studies in cells and animal models of MBL mediated-injuries. This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska- Curie grant agreement No 814236. The authors wish to thank Mrs. Judith Baggott for English stylistic editing.

BACKGROUND: Anti-PD-(L)1 therapy alone (cancer immunotherapy [CIT]-mono) or combined with platinum-based chemotherapy (CIT-chemo) is used as first-line treatment for patients with metastatic non-small cell lung cancer (NSCLC). Our study compared clinical outcomes with CIT-mono vs CIT-chemo in the specific clinical scenario of non-squamous (Nsq)-NSCLC with a high PD-L1 expression of ≥50\% (tumor proportion score (TPS) or tumor cells (TC)). METHODS: This was a retrospective cohort study using a real-world de-identified database. Patients with metastatic Nsq-NSCLC with high PD-L1 expression initiating first-line CIT-mono or CIT-chemo between 24 October 2016 and 28 February 2019 were followed up to 28 February 2020. We compared overall survival (OS) and real-world progression-free survival (rwPFS) using Kaplan-Meier methodology. Hazard ratios (HR) were adjusted (aHR) for differences in baseline key prognostic characteristics using inverse probability of treatment weighting methodology. RESULTS: Patients with PD-L1-high Nsq-NSCLC treated with CIT-mono (n=351), were older and less often presented with de novo stage IV disease than patients treated with CIT-chemo (n=169). With a median follow-up of 19.9 months for CIT-chemo vs 23.5 months for CIT-mono, median OS and rwPFS did not differ between the two groups (median OS: CIT-chemo, 21.0 months vs CIT-mono, 22.1 months, aHR=1.03, 95\% CI 0.77-1.39, P=0.83; median rwPFS: CIT-chemo, 10.8 months vs CIT-mono, 11.5 months, aHR=1.04, 95\% CI 0.78-1.37, P=0.81). CIT-chemo showed significant and meaningful improvement in OS and rwPFS vs CIT-mono only in the never-smoker subgroup, albeit among a small sample of patients (n=50; OS HR=0.25, 95\% CI 0.07-0.83, interaction P=0.02; rwPFS HR=0.40, 95\% CI 0.17-0.95, interaction P=0.04). CONCLUSION: Except in the subgroup of never-smoker patients, sparing the chemotherapy in first-line CIT treatment does not appear to impact survival outcomes in Nsq-NSCLC patients with high PD-L1 expression.

Vaccination is one of the greatest achievements in biomedical research preventing death and morbidity in many infectious diseases through the induction of pathogen-specific humoral and cellular immune responses. Currently, no effective vaccines are available for pathogens with a highly variable antigenic load, such as the human immunodeficiency virus or to induce cellular T-cell immunity in the fight against cancer. The recent SARS-CoV-2 outbreak has reinforced the relevance of designing smart therapeutic vaccine modalities to ensure public health. Indeed, academic and private companies have ongoing joint efforts to develop novel vaccine prototypes for this virus. Many pathogens are covered by a dense glycan-coat, which form an attractive target for vaccine development. Moreover, many tumor types are characterized by altered glycosylation profiles that are known as "tumor-associated carbohydrate antigens". Unfortunately, glycans do not provoke a vigorous immune response and generally serve as T-cell-independent antigens, not eliciting protective immunoglobulin G responses nor inducing immunological memory. A close and continuous crosstalk between glycochemists and glycoimmunologists is essential for the successful development of efficient immune modulators. It is clear that this is a key point for the discovery of novel approaches, which could significantly improve our understanding of the immune system. In this review, we discuss the latest advancements in development of vaccines against glycan epitopes to gain selective immune responses and to provide an overview on the role of different immunogenic constructs in improving glycovaccine efficacy. European Cooperation in Science and Technology (COST) CA18103 Ministry of Education, Youth & Sports - Czech Republic CA18103 LTC20078

Page 363, affiliations section, “On behalf of the ICARA Study Group” should instead read “and the ICARA study group”.

International audience; BACKGROUND : Changes in criteria and differences in populations studied and methodology have produced a wide range of prevalence estimates for mild cognitive impairment (MCI).METHODS : Uniform criteria were applied to harmonized data from 11 studies from USA, Europe, Asia and Australia, and MCI prevalence estimates determined using three separate definitions of cognitive impairment.RESULTS : The published range of MCI prevalence estimates was 5.0%-36.7%. This was reduced with all cognitive impairment definitions: performance in the bottom 6.681% (3.2%-10.8%); Clinical Dementia Rating of 0.5 (1.8%-14.9%); Mini-Mental State Examination score of 24-27 (2.1%-20.7%). Prevalences using the first definition were 5.9% overall, and increased with age (P < .001) but were unaffected by sex or the main races/ethnicities investigated (Whites and Chinese). Not completing high school increased the likelihood of MCI (P ≤ .01).CONCLUSION : Applying uniform criteria to harmonized data greatly reduced the variation in MCI prevalence internationally.

At present, mammary carcinoma is the second most common type of malignant tumor in adult women after lung cancer, as more than one million women are diagnosed with breast cancer every year. Despite advances in diagnosis and treatment, which have resulted in a decrease in mortality in recent decades, breast cancer remains a major public health problem. One of the most significant unresolved clinical and scientific problems is the occurrence of resistance to clinical treatments and their toxicity (and how to predict, prevent and overcome them). However, the heterogeneity of human breast cancer in terms of genetic features, molecular profiles and clinical behavior represents a constraint obstructing the discovery of a solution to the disease. It is currently considered that the chances of success of therapy may increase if the tumor cells are selectively removed before they can evolve to their mature stages up to metastases production. Therefore, novel and more sensitive diagnostic tools are being developed, with the aim of improving the early and noninvasive detection of rising malignancies and the accuracy of tumor tissue localization. Meanwhile, there is an emerging use of targeted therapies in oncology, depending on the expression of specific proteins or genes present in tumor cells. Among the molecular targets considered for the treatment of breast cancer cells so far, we chose to focus on examples involving overexpression and/or gene amplification of "Human Epidermal growth factor Receptor 2" (HER2) protein. In current studies, various types of nanoparticles conjugated with the anti-HER2 monoclonal antibody, the so-called "trastuzumab", are investigated extensively due to promising results in biological and preclinical applications aimed at improving the treatment of breast cancer. In this paper, we present a critical review of the preparation and use of different kinds of trastuzumab-functionalized nanoparticles, with an emphasis on the therapeutic and diagnostic (theranostic) potential of this generation of hybrid nanoparticles, exploiting the multifaceted mechanisms of action of trastuzumab against malignant cells. (c) 2010 Elsevier Ltd. All rights reserved.

Neisseria meningitidis is a Gram-negative encapsulated bacterium that is a major cause of meningitis and meningococcal septicemia. Serogroup A (MenA) is most often implicated in epidemic disease in the sub-Saharan region of Africa. However, the development and manufacture of an efficient polysaccharide-based vaccine against MenA is greatly hampered by the poor immunogenicity and instability of its capsular polisaccharide (CPS). We report the synthesis of stable MenA CPS carba analogues, and an easy strategy to access multivalent carbohydrate structures based on iron oxide nanoparticles (SPIONs). A 1-O-tetraethyleneglycol-phosphate linker attached to the carba analogues was used to attach them to the metal surface. We evaluated the positive multivalent effect of the antigen presentation by MRI analysis, which showed that the conjugated monomer and dimer analogues could be recognised by the polyclonal anti-MenA antibody. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A major challenge in magnetic nanoparticle synthesis and (bio)functionalization concerns the precise characterization of their surface ligands. We report the first analytical NMR investigation of organic ligands stably anchored on the surface of superparamagnetic nanoparticles (MNPs) through the development of a new experimental application of high-resolution magic angle spinning (HRMAS). The conceptual advance here is that HRMAS technique, already being used for MAS NMR analysis of gels and semi-solid matrices, enables the fine structure-resolved characterization of even complex organic molecules bound to paramagnetic nanocrystals, such as nanosized iron oxides, by strongly decreasing the effects of paramagnetic disturbances. This method led to detail-rich, well-resolved 1H NMR spectra, often with highly structured first-order couplings, essential in the interpretation of the data. This HRMAS application was first evaluated and optimized using simple ligands widely used as surfactants in MNP synthesis and conjugation. Next, the methodology was assessed through the structure determination of complex molecular architectures, such as those involved in MNP3 and MNP4. The comparison with conventional probes evidences that HRMAS makes it possible to work with considerably higher concentrations, thus avoiding the loss of structural information. Consistent 2D homonuclear 1H-1H (COSY) and 1H-13C heteronuclear single quantum coherence (HSQC) correlation spectra were also obtained, providing reliable elements on proton signal assignments and carbon characterization, and opening the way to the 13C NMR determination. Notably, combining the experimental evidences from HRMAS 1H NMR and diffusion-ordered spectroscopy (DOSY) performed on the hybrid nanoparticle dispersion confirmed that the ligands were tightly bound to the particle surface when they were dispersed in a ligand-free solvent, while they rapidly exchanged when an excess of free ligand was present in solution. In addition to HRMAS NMR, MALDI-TOF MS analysis of modified MNPs proved very valuable in ligand mass identification, thus giving a sound support to NMR characterization achievements.