GMMA decorated with mucin 1 Tn/STn mimetics elicit specific antibodies response and inhibit tumor growth.

Carbohydrate-based therapeutic vaccines are actively pursued as targeted immunotherapy to treat cancer. Aberrant glycosylation is indeed of paramount importance in tumors, leading to the formation of "neo-epitopes", known as tumor-associated carbohydrate antigens (TACAs), crucial in cancer onset, development and spread. Accordingly, the over-simplified mucin-type O-glycans Tn and STn have been confirmed among the most promising candidates for the development of cancer vaccines.

Detection of Tumor-Associated Autoantibodies in the Sera of Pancreatic Cancer Patients Using Engineered MUC1 Glycopeptide Nanoparticle Probes.

Pancreatic cancer is one of the deadliest cancers worldwide, mainly due to late diagnosis. Therefore, there is an urgent need for novel diagnostic approaches to identify the disease as early as possible. We have developed a diagnostic assay for pancreatic cancer based on the detection of naturally occurring tumor associated autoantibodies against Mucin-1 (MUC1) using engineered glycopeptides on nanoparticle probes.

Polysaccharides' Structures and Functions in Biofilm Architecture of Antimicrobial-Resistant (AMR) Pathogens.

Bacteria and fungi have developed resistance to the existing therapies such as antibiotics and antifungal drugs, and multiple mechanisms are mediating this resistance. Among these, the formation of an extracellular matrix embedding different bacterial cells, called biofilm, is an effective strategy through which bacterial and fungal cells are establishing a relationship in a unique environment. The biofilm provides them the possibility to transfer genes conferring resistance, to prevent them from desiccation and to impede the penetration of antibiotics or antifungal drugs.

Niosomes as Biocompatible Scaffolds for the Multivalent Presentation of Tumor-Associated Antigens (TACAs) to the Immune System.

Fully synthetic tumor-associated carbohydrate antigen (TACA)-based vaccines are a promising strategy to treat cancer. To overcome the intrinsic low immunogenicity of TACAs, the choice of the antigens' analogues and multivalent presentation have been proved to be successful. Here, we present the preparation, characterization, and screening of niosomes displaying multiple copies of the mucin antigen TnThr (niosomes-) or of TnThr mimetic (niosomes-).

Probing the Efficiency of 13-Pyridylalkyl Berberine Derivatives to Human Telomeric G-Quadruplexes Binding: Spectroscopic, Solid State and In Silico Analysis.

The interaction between the series of berberine derivatives - (NAX071, NAX120, NAX075, NAX077 and NAX079) and human telomeric G-quadruplexes (G4), which are able to inhibit the Telomerase enzyme's activity in malignant cells, was investigated. The derivatives bear a pyridine moiety connected by a hydrocarbon linker of varying length ( = 1-5, with number of aliphatic carbon atoms) to the C13 position of the parent berberine. As for the G4s, both bimolecular 5'-TAGGGTTAGGGT-3' (Tel12) and monomolecular 5'-TAGGGTTAGGGTTAGGGTTAGGG-3' (Tel23) DNA oligonucleotides were considered.

Structurally Constrained MUC1-Tn Mimetic Antigen as Template for Molecularly Imprinted Polymers (MIPs): A Promising Tool for Cancer Diagnostics.

Abnormal glycoconjugates have distinctly been recognized as potential biomarkers for cancer diagnosis. A great deal of attention has been focused on Tn antigen, an oversimplified mucin-1 O-glycan, over-expressed in different cancers. Herein, we investigate the possibility to replace the use of anti-Tn monoclonal antibodies with an innovative class of catecholamine-based Molecularly Imprinted Polymers (MIPs), emerging in recent years as promising tools for bioanalytical applications.

Conformationally Constrained Sialyl Analogues as New Potential Binders of h-CD22.

Here, two conformationally constrained sialyl analogues were synthesized and characterized in their interaction with the inhibitory Siglec, human CD22 (h-CD22). An orthogonal approach, including biophysical assays (SPR and fluorescence), ligand-based NMR techniques, and molecular modelling, was employed to disentangle the interaction mechanisms at a molecular level. The results showed that the Sialyl-TnThr antigen analogue represents a promising scaffold for the design of novel h-CD22 inhibitors.

Recent advances and future perspectives on carbohydrate-based cancer vaccines and therapeutics.

Carbohydrates are abundantly expressed on the surface of both eukaryotic and prokaryotic cells, often as post translational modifications of proteins. Glycoproteins are recognized by the immune system and can trigger both innate and humoral responses. This feature has been harnessed to generate vaccines against polysaccharide-encapsulated bacteria such as Streptococcus pneumoniae, Hemophilus influenzae type b and Neisseria meningitidis.

A Sulfonated Tweezer-Shaped Receptor Selectively Recognizes Caffeine in Water.

The selective recognition of caffeine in water among structurally related xanthines and purine or pyrimidine bases was achieved by a simple tweezer-shaped receptor featuring sulfonate hydrosolubilizing groups. The remarkable affinity for caffeine, among the highest reported thus far in the literature and larger than that shown by adenosine receptors of all subtypes, stems from a synergistic combination of hydrogen bonding, CH-π, and π-stacking interactions.

Sustainability of Rearing System Using Multicriteria Analysis: Application in Commercial Poultry Production.

The aim of the present study was to develop a multicriteria model for the comparison of three commercial poultry farms: organic with Ross 308 genotype (OR), organic with Naked Neck genotype (ONN) and a conventional system (C), which represents the most common commercial farming system. A model based on multicriteria decision analysis was developed, considering for the first time the One Welfare approach in an operational manner, including three dimensions: human, environmental and animal welfare. The three alternatives demonstrated different performances, according to the different dimensions considered.

Association between Ideal Cardiovascular Health and aortic stiffness in Italian adolescents. The MACISTE study.

Background And Aims: Ideal Cardiovascular Health (ICH), defined as optimal levels of cardiovascular (CV) health factors and behaviors, has been reported to be very low in adults and children, with consequent several negative health outcomes and higher CV risk. The present study investigated the burden of ICH among Italian adolescents and its association with carotid-femoral pulse wave velocity (cf-PWV).

Methods And Results: 387 healthy adolescents (mean age 17.

Synthesis of an STnThr analogue, structurally based on a TnThr antigen mimetic.

The monosaccharide Tn and the disaccharide STn are tumor antigens with similar structures and common biosynthetic pathways. Both are always over-expressed simultaneously on tumor cell surfaces. We report herein the efficient synthesis of the STnThr antigen analogue 2, featuring the immunogenic TnThr mimetic 1 aglycon.

Correction to "Pyridine Derivative of the Natural Alkaloid Berberine as Human Telomeric G-DNA Binder: A Solution and Solid-State Study".

[This corrects the article DOI: 10.1021/acsmedchemlett.9b00516.

A Structurally Simple Vaccine Candidate Reduces Progression and Dissemination of Triple-Negative Breast Cancer.

The Tn antigen is a well-known tumor-associated carbohydrate determinant, often incorporated in glycopeptides to develop cancer vaccines. Herein, four copies of a conformationally constrained mimetic of the antigen TnThr (GalNAc-Thr) were conjugated to the adjuvant CRM197, a protein licensed for human use. The resulting vaccine candidate, mime[4]CRM elicited a robust immune response in a triple-negative breast cancer mouse model, correlated with high frequency of CD4+ T cells and low frequency of M2-type macrophages, which reduces tumor progression and lung metastasis growth.

Pyridine Derivative of the Natural Alkaloid Berberine as Human Telomeric G-DNA Binder: A Solution and Solid-State Study.

Telomerase is an enzyme deputed to the maintenance of eukaryotic chromosomes; however, its overexpression is a recognized hallmark of many cancer forms. A viable route for the inhibition of telomerase in malignant cells is the stabilization of G-quadruplex structures (G) at the 3' overhang of telomeres. Berberine has shown in this regard valuable G binding properties together with a significant anticancer activity and telomerase inhibition effects.

Tn antigen analogues: the synthetic way to "upgrade" an attracting tumour associated carbohydrate antigen (TACA).

In the last two decades, the paramount importance of Tumor Associated Carbohydrate Antigens (TACAs) as targets for anticancer vaccine development has been firmly assessed. The Tn antigen is an ideal target for immunotherapy, in that it is masked on normal cells, but exposed on cancer cells. However, it is difficult to elicit an effective and long-lasting response against Tn antigen and other TACAs.

Effect of structure levels on surface-enhanced Raman scattering of human telomeric G-quadruplexes in diluted and crowded media.

Human telomeric G-quadruplexes are emerging targets in anticancer drug discovery since they are able to efficiently inhibit telomerase, an enzyme which is greatly involved in telomere instability and immortalization process in malignant cells. G-quadruplex (G4) DNA is highly polymorphic and can adopt different topologies upon addition of electrolytes, additives, and ligands. The study of G-quadruplex forms under various conditions, however, might be quite challenging.

Induction of a Four-Way Junction Structure in the DNA Palindromic Hexanucleotide 5'-d(CGTACG)-3' by a Mononuclear Platinum Complex.

Four-way junctions (4WJs) are supramolecular DNA assemblies comprising four interacting DNA strands that in biology are involved in DNA-damage repair. In this study, a new mononuclear platinum(II) complex 1 was prepared that is capable of driving the crystallization of the DNA oligomer 5'-d(CGTACG)-3' specifically into a 4WJ-like motif. In the crystal structure of the 1-CGTACG adduct, the distorted-square-planar platinum complex binds to the core of the 4WJ-like motif through π-π stacking and hydrogen bonding, without forming any platinum-nitrogen coordination bonds.

Interaction of a gold(i) dicarbene anticancer drug with human telomeric DNA G-quadruplex: solution and computationally aided X-ray diffraction analysis.

The bis carbene gold(i) complex [Au(1-butyl-3-methyl-2-ylidene)2]PF6, ([Au(NHC)2]PF6 hereafter), holds remarkable interest as a perspective anticancer agent. The compound is stable under physiological like conditions: its original structure is retained even in the presence of excess glutathione (GSH). Previous studies revealed its high cytotoxicity in vitro that correlates with the impairment of crucial metabolic and enzymatic cellular processes (Magherini et al.

[Au(9-methylcaffein-8-ylidene) ] /DNA Tel23 System: Solution, Computational, and Biological Studies.

Physicochemical methods have been used to investigate interactions occurring in solution between the dicarbene gold(I) complex [Au(9-methylcaffein-8-ylidene) ]BF (AuNHC) and a human telomeric DNA sequence, namely Tel23. Circular dichroism measurements allow identification of the conformational changes experienced by Tel23 upon interaction with AuNHC, and the respective binding stoichiometries and constants were determined. Computational studies provide a good link between previous crystallographic results of the same system and the present solution data, offering an exhaustive description of the inherent noncovalent metallodrug-DNA interactions.

Solution NMR Structure of a Ligand/Hybrid-2-G-Quadruplex Complex Reveals Rearrangements that Affect Ligand Binding.

Telomeric G-quadruplexes have recently emerged as drug targets in cancer research. Herein, we present the first NMR structure of a telomeric DNA G-quadruplex that adopts the biologically relevant hybrid-2 conformation in a ligand-bound state. We solved the complex with a metalorganic gold(III) ligand that stabilizes G-quadruplexes.

Fetuin-A, adiposity-linked insulin resistance and responsiveness to an educational-based weight excess reduction program: a population-based survey in prepubertal schoolchildren.

The secreted hepatokine fetuin-A emerges as an independent predictor of type 2 diabetes in adulthood. The overall aims of this study were: (1) to investigate the associations of fetuin-A with adiposity and insulin resistance, as well as its relationship with adipokines, in prepubertal children, and, (2) to evaluate whether, in prepubertal obesity, serum fetuin-A levels may either change or predict the responsiveness to an educational-based weight excess reduction program. We studied 200 prepubertal children (boys/girls: 89/111; Tanner stage 1; age: 5-13 years), included in a cohort of 44,231 adolescents who participated in an extensive Italian school-based survey.

Determinants for Tight and Selective Binding of a Medicinal Dicarbene Gold(I) Complex to a Telomeric DNA G-Quadruplex: a Joint ESI MS and XRD Investigation.

The dicarbene gold(I) complex [Au(9-methylcaffein-8-ylidene)2 ]BF4 is an exceptional organometallic compound of profound interest as a prospective anticancer agent. This gold(I) complex was previously reported to be highly cytotoxic toward various cancer cell lines in vitro and behaves as a selective G-quadruplex stabilizer. Interactions of the gold complex with various telomeric DNA models have been analyzed by a combined ESI MS and X-ray diffraction (XRD) approach.

Solution and Solid-State Analysis of Binding of 13-Substituted Berberine Analogues to Human Telomeric G-quadruplexes.

The interaction between 13-phenylalkyl and 13-diphenylalkyl berberine derivatives (NAX) and human telomeric DNA G4 structures has been investigated by both spectroscopic and crystallographic methods. NAX042 and NAX053 are the best compounds improving the performance of the natural precursor berberine. This finding is in agreement with the X-ray diffraction result for the NAX053-Tel12 adduct, showing the ligand which interacts via π-stacking, sandwiched at the interface of two symmetry-related quadruplex units, with its benzhydryl group contributing to the overall stability of the adduct by means of additional π-stacking interactions with the DNA residues.

Inflammatory adipokines, high molecular weight adiponectin, and insulin resistance: a population-based survey in prepubertal schoolchildren.

Background: The aim of this study was to investigate sex differences and associations of high molecular weight (HMW) adiponectin, leptin and proinflammatory adipokines, individually or in combinations, with adiposity and insulin resistance (IR) measures in prepubertal childhood.

Methodology: We studied 305 prepubertal children (boys/girls: 144/161; Tanner stage 1; age: 5-13 yr), included in a cohort of 44,231 adolescents who participated in an extensive Italian school-based survey. According to Cole's criteria, 105 individuals were lean (L; boys/girls: 59/46), 60 overweight (OW; boys/girls: 32/28) and 140 obese (OB; boys/girls: 70/70).