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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

Amanita fungi are the main lethal toadstool among the 1000 poisonous mushrooms known in the world. Thrombin is the key serine proteinase of the coagulation cascade and therefore a suitable target for inhibition of blood coagulation. An extract of Amanita virosa considerably inhibited thrombin (48%) and showed no inhibitory activity on trypsin. On the basis of inhibition selectivity between thrombin and trypsin and potency of thrombin inhibition, Amanita virosa constituted a good starting material for isolation of further compounds that are active against thrombin. In a preliminary study, 95 selected mushroom species have been screened in order to find novel specific non-peptidic thrombin inhibitors. The extract of Amanita virosa considerably inhibited thrombin (48% at concentration of 120 μg/mL). A bioassay oriented fractionation of the extract of Amanita virosa has led to the isolation of active compounds. On the basis of spectroscopic data, chemical reactions and GCMS analysis, complex mixtures of triglycerides, monoacylglycerols, free fatty acids and ergosterol have been isolated and identified.

Sponges of the genus Agelas produce compounds that modulate the activity of voltage-gated sodium ion channels and contribute novel scaffolds for the development of compounds with activity against a plethora of biological targets. In particular, clathrodin and dibromosceptrin were reported to decrease the average maximum amplitude of inward sodium currents in isolated chick embryo sympathetic ganglia cells; we envisaged these compounds as a starting point to design novel Na-v channel modulators. This endeavor was part of our long-term goal of designing a comprehensive library of Agelas alkaloid analogs that would cover a broader chemical space and allow us to examine the activity of such compounds on Na-v channels. Our series of compounds was designed by maintaining the terminal structural features found in clathrodin while rigidizing the central part of the molecule and replacing the 3-aminopropene linker with a 4-methylenepiperazine moiety. Synthesised compounds were screened for inhibitory action against the human voltage-gated sodium channel isoforms Na-v 1.3, Na-v 1.4, cardiac Na-v 1.5, and Na-v 1.7 using an automated patch clamp electrophysiology technique. The results demonstrate that we have obtained a series of compounds with a modest but selective inhibitory activity against the Na-v 1.3 channel isoform. The most potent compound showed selective activity against the Na-v 1.3 channel isoform with an IC50 of 19 mu M and is a suitable starting point for further development of selective Na-v 1.3 channel modulators. Such compounds could prove to be beneficial as a pharmacological tool towards the development of novel therapeutically useful compounds in the treatment of pain.

The objective of this study was to examine whether there is an association between individual and family eating patterns during childhood and early adolescence and the likelihood of developing a subsequent eating disorder (ED). A total of 1664 participants took part in the study. The ED cases (n 879) were referred for assessment and treatment to specialized ED units in five different European countries and were compared to a control group of healthy individuals (n 785). Participants completed the Early Eating Environmental Subscale of the Cross-Cultural (Environmental) Questionnaire, a retrospective measure, which has been developed as part of a European multicentre trial in order to detect dimensions associated with ED in different countries. In the control group, also the General Health Questionnaire-28 (GHQ-28), the semi-structured clinical interview (SCID-I) and the Eating Attitudes Test (EAT-26) were used. Five individually Categorical Principal Components Analysis (CatPCA) procedures were adjusted, one for each theoretically expected factor. Logistic regression analyses indicated that the domains with the strongest effects from the CatPCA scores in the total sample were: food used as individualization, and control and rules about food. Oil the other hand, healthy eating was negatively related to a subsequent ED. When differences between countries were assessed, results indicated that the pattern of associated ED factors did vary between countries. There was very little difference in early eating behaviour on the subtypes of ED. These findings suggest that the fragmentation of meals within the family and an excessive importance given to food by the individual and the family are linked to the later development of an ED.

Objectives: To assess the differences in comorbid lifetime and current substance use (tobacco, alcohol and drug use) between eating disorder (ED) patients and healthy controls in five different European countries. Method: A total of 1664 participants took part in the present study. ED cases (n=879) were referred to specialized ED units in five European countries. The ED cases were compared to a balanced control group of 785 healthy individuals. Assessment: Participants completed the Substance Use Subscale of the Cross Cultural (Environmental) Questionnaire (CCQ), a measure of lifetime tobacco, alcohol and drug use. In the control group, also the GHQ-28, the SCID-1 interview and the EAT-26 were used. Results: ED patients had higher lifetime and current tobacco and general drug use. The only non-significant result was obtained for lifetime and current alcohol use. Significant differences across ED subdiagnoses and controls also emerged, with BN and AN-BP generally presenting the highest and AN-R and controls the lowest rates. The only exception was detected for alcohol use where EDNOS demonstrated the highest values. Only a few cultural differences between countries emerged. Conclusions: With the exception of alcohol consumption, tobacco and drug use appear to be more prevalent in ED patients than healthy controls. The differential risk observed in patients with bulimic features might be related to differences in temperament or might be the result of increased sensitivity to reward. (C) 2008 Elsevier Ireland Ltd. All rights reserved.

Glycan structures are common posttranslational modifications of proteins, which serve multiple important structural roles (for instance in protein folding), but also are crucial participants in cell–cell communications and in the regulation of immune responses. Through the interaction with glycan‐binding receptors, glycans are able to affect the activation status of antigen‐presenting cells, leading either to induction of pro‐inflammatory responses or to suppression of immunity and instigation of immune tolerance. This unique feature of glycans has attracted the interest and spurred collaborations of glyco‐chemists and glyco‐immunologists to develop glycan‐based tools as potential therapeutic approaches in the fight against diseases such as cancer and autoimmune conditions. In this review, we highlight emerging advances in this field, and in particular, we discuss on how glycan‐modified conjugates or glycoengineered cells can be employed as targeting devices to direct tumor antigens to lectin receptors on antigen‐presenting cells, like dendritic cells. In addition, we address how glycan‐based nanoparticles can act as delivery platforms to enhance immune responses. Finally, we discuss some of the latest developments in glycan‐based therapies, including chimeric antigen receptor (CAR)‐T cells to achieve targeting of tumor‐associated glycan‐specific epitopes, as well as the use of glycan moieties to suppress ongoing immune responses, especially in the context of autoimmunity., Glycans are macromolecules that perform crucial roles in development, in cell–cell communication, and in the regulation of immune responses. In this review, we highlight how glycans can be exploited and empowered as treatment or vaccine modalities, particularly in the fight against cancer and autoimmune diseases.

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.

Objective: To explore the psychometric properties of the Cross-Cultural Questionnaire (CCQ), a new self-report tool for assessing factors of risk and maintenance for eating disorders (ED). Method: Data was collected during a multi-centre case-control study. The sample included 854 ED patients and 784 healthy participants from the UK, Spain, Austria, Slovenia and Italy. Exploratory factor analyses examined the factor structure of each section of the CCQ, and Cronbach's alpha coefficients valued the internal consistency of each derived scale score. Logistic regression and receiver operating characteristic (ROC) curve procedure assessed the screening accuracy and predictive validity of the empirical factors. Results: Based on a total of 127 items, nine dimensions emerged, with satisfactory internal consistency and high congruence between countries. CCQ scores demonstrated satisfactory accuracy for discriminating between ED cases and controls (area under the ROC curve = 0.88). Most of the items achieved discriminative accuracy. Conclusions: This study offers preliminary evidence that the CCQ, available in five languages, is a useful and valid tool to assess factors of risk and maintenance for EDs. Copyright © 2010 John Wiley & Sons, Ltd. Key Practitioner Message: • The CCQ is a new self-report questionnaire for assessing factors of risk and maintenance for eating disorders. • The CCQ is available in five languages (Spanish, English, German, Italian and Slovenian) and is free of charge for research purposes. • CCQ scores demonstrated satisfactory accuracy for discriminating between ED cases and controls.

Objective To examine a new socio-family risk model of Eating Disorders (EDs) using path-analyses. Method The sample comprised 1264 (ED patients = 653; Healthy Controls = 611) participants, recruited into a multicentre European project. Socio-family factors assessed included: perceived maternal and parental parenting styles, family, peer and media influences, and body dissatisfaction. Two types of path-analyses were run to assess the socio-family model: 1.) a multinomial logistic path-model including ED sub-types [Anorexia Nervosa-Restrictive (AN-R), AN-Binge-Purging (AN-BP), Bulimia Nervosa (BN) and EDNOS)] as the key polychotomous categorical outcome and 2.) a path-model assessing whether the socio-family model differed across ED sub-types and healthy controls using body dissatisfaction as the outcome variable. Results The first path-analyses suggested that family and media (but not peers) were directly and indirectly associated (through body dissatisfaction) with all ED sub-types. There was a weak effect of perceived parenting directly on ED sub-types and indirectly through family influences and body dissatisfaction. For the second path-analyses, the socio-family model varied substantially across ED sub-types. Family and media influences were related to body dissatisfaction in the EDNOS and control sample, whereas perceived abusive parenting was related to AN-BP and BN. Discussion This is the first study providing support for this new socio-family model, which differed across ED sub-types. This suggests that prevention and early intervention might need to be tailored to diagnosis-specific ED profiles.

Two new triterpene acids (1, 2), together with a complex mixture of lecithins (3), were isolated from the fungus Gloeophyllum odoratum. Their structures were elucidated on the basis of extensive spectroscopic analyses. The extract of Gloeophyllum odoratum considerably inhibited thrombin (72% at a concentration of 120 μg/mL); the less polar fraction of the methanolic extract from the mushroom exhibited interesting activity (47% at a concentration of 120 μg/mL) against thrombin. Compounds 1 and 2 were responsible for this activity.

Eating disorders (ED), such as anorexia nervosa (AN) and bulimia nervosa (BN), are complex psychiatric disorders where different genetic and environmental factors are involved. Several lines of evidence support that brain-derived neurotrophic factor (BDNF) plays an essential role in eating behaviour and that alterations on this neurotrophic system participates in the susceptibility to both AN and BN. Accordingly, intraventricular administration of BDNF in rats determines food starvation and body weight loss, while BDNF or its specific receptor NTRK2 knockout mice develop obesity and hyperphagia. Case-control studies also suggest a BDNF contribution in the aetiology of ED: we have previously reported a strong association between the Met66 variant within the BDNF gene, restricting AN (ANR) and minimum body mass index (minBMI) in a Spanish sample, and a positive association between the Val66Met and -270C/T BDNF SNPs and ED in six different European populations. To replicate these results, avoiding population stratification effects, we recruited 453 ED trios from eight European centres and performed a family-based association study. Both haplotype relative risk (HRR) and haplotype-based haplotype relative risk (HHRR) methods showed a positive association between the Met66 allele and ANR. Consistently, we also observed an effect of the Met66 variant on low minBMI and a preferential transmission of the -270C/Met66 haplotype to the affected ANR offspring. These results support the involvement of BDNF in eating behaviour and further suggest its participation in the genetic susceptibility to ED, mainly ANR and low minBMI. © 2005 Nature Publishing Group All rights reserved.

Thrombin is the key serine proteinase of the coagulation cascade and, therefore, a suitable target for inhibition of blood coagulation. An extract of Amanita virosa considerably inhibited thrombin (48%), but showed no inhibitory activity on trypsin. On the basis of inhibition selectivity between thrombin and trypsin and potency of thrombin inhibition, A. virosa constitutes a good starting material for the isolation of further compounds that are active against thrombin. Bioassay oriented fractionation of the extract of A. virosa led to the isolation of a complex mixture of triglycerides (TGs), monoacylglycerols (MAGs), free fatty acids (FAs) and ergosterol. The structures of the isolated lipids metabolites were determined on the basis of chemical and spectroscopic evidences.