Epigenetic Properties of Compounds Contained in Functional Foods Against Cancer.

Epigenetics encompasses reversible and heritable genomic changes in histones, DNA expression, and non-coding RNAs that occur without modifying the nucleotide DNA sequence. These changes play a critical role in modulating cell function in both healthy and pathological conditions. Dysregulated epigenetic mechanisms are implicated in various diseases, including cardiovascular disorders, neurodegenerative diseases, obesity, and mainly cancer.

Overexpression of Glyoxalase 2 in Human Breast Cancer Cells: Implications for Cell Proliferation and Doxorubicin Resistance.

Glyoxalase 2 (Glo2) is an enzyme of the glyoxalase system whose pathway parallels glycolysis and which aims to remove methylglyoxal (MGO). This study analyzed the possible additional roles of the Glo2 enzyme in breast cancer (MCF7) and non-cancer (HDF) cell lines, investigating its presence at the nuclear level and its potential involvement in cell proliferation and chemotherapy resistance. The results revealed that Glo2 is overexpressed in cancer cells, and its expression is higher during the proliferative (S and G2/M) phases of the cell cycle.

Emergence and Criticality in Spatiotemporal Synchronization: The Complementarity Model.

This work concerns the long-term collective excitability properties and the statistical analysis of the critical events displayed by a recently introduced spatiotemporal many-body model, proposed as a new paradigm for Artificial Life. Numerical simulations show that excitable collective structures emerge in the form of dynamic networks, created by bursts of spatiotemporal activity (avalanches) at the edge of a synchronization phase transition. The spatiotemporal dynamics is portraited by a movie and quantified by time varying collective parameters, showing that the dynamic networks undergo a "life cycle," made of self-creation, homeostasis, and self-destruction.

Glutathionyl Hemoglobin and Its Emerging Role as a Clinical Biomarker of Chronic Oxidative Stress.

Hemoglobin is one of the proteins that are more susceptible to S-glutathionylation and the levels of its modified form, glutathionyl hemoglobin (HbSSG), increase in several human pathological conditions. The scope of the present review is to provide knowledge about how hemoglobin is subjected to S-glutathionylation and how this modification affects its functionality. The different diseases that showed increased levels of HbSSG and the methods used for its quantification in clinical investigations will be also outlined.

The emergence of dynamic networks from many coupled polar oscillators: a paradigm for artificial life.

This work concerns a many-body deterministic model that displays life-like properties such as emergence, complexity, self-organization, self-regulation, excitability and spontaneous compartmentalization. The model portraits the dynamics of an ensemble of locally coupled polar phase oscillators, moving in a two-dimensional space, that under certain conditions exhibit emergent superstructures. Those superstructures are self-organized dynamic networks, resulting from a synchronization process of many units, over length scales much greater than the interaction range.

Glyoxalase 2: Towards a Broader View of the Second Player of the Glyoxalase System.

Glyoxalase 2 is a mitochondrial and cytoplasmic protein belonging to the metallo-β-lactamase family encoded by the hydroxyacylglutathione hydrolase (HAGH) gene. This enzyme is the second enzyme of the glyoxalase system that is responsible for detoxification of the α-ketothaldehyde methylglyoxal in cells. The two enzymes glyoxalase 1 (Glo1) and glyoxalase 2 (Glo2) form the complete glyoxalase pathway, which utilizes glutathione as cofactor in eukaryotic cells.

Complement-mediated serum bactericidal activity of antibodies elicited by the GMMA vaccine in adults from a shigellosis-endemic country: Exploratory analysis of a Phase 2a randomized study.

is associated with a significant burden of disease worldwide among individuals of all ages and is the major cause of moderate and severe diarrhea in children under five years of age in low- and middle-income countries. Several candidate vaccines against species are currently under clinical development. The investigational 1790GAHB vaccine against is based on GMMA (Generalized Modules for Membrane Antigens) technology.

Antibodies Elicited by the GMMA Vaccine in Adults Trigger Complement-Mediated Serum Bactericidal Activity: Results From a Phase 1 Dose Escalation Trial Followed by a Booster Extension.

is the second most deadly diarrheal disease among children under five years of age, after rotavirus, with high morbidity and mortality in developing countries. Currently, no vaccine is widely available, and the increasing levels of multidrug resistance make a high priority for vaccine development. The single-component candidate vaccine against (1790GAHB), developed using the GMMA technology, contains the O antigen (OAg) portion of lipopolysaccharide (LPS) as active moiety.

The Role of Artificial Intelligence in the Diagnosis and Prognosis of Renal Cell Tumors.

The increasing availability of molecular data provided by next-generation sequencing (NGS) techniques is allowing improvement in the possibilities of diagnosis and prognosis in renal cancer. Reliable and accurate predictors based on selected gene panels are urgently needed for better stratification of renal cell carcinoma (RCC) patients in order to define a personalized treatment plan. Artificial intelligence (AI) algorithms are currently in development for this purpose.

Interplay among Oxidative Stress, Methylglyoxal Pathway and S-Glutathionylation.

Reactive oxygen species (ROS) are produced constantly inside the cells as a consequence of nutrient catabolism. The balance between ROS production and elimination allows to maintain cell redox homeostasis and biological functions, avoiding the occurrence of oxidative distress causing irreversible oxidative damages. A fundamental player in this fine balance is reduced glutathione (GSH), required for the scavenging of ROS as well as of the reactive 2-oxoaldehydes methylglyoxal (MGO).

Improved Pregnancy Outcome in Patients With Rheumatoid Arthritis Who Followed an Ideal Clinical Pathway.

Objective: To assess the effect of optimal management of pregnancy on a composite outcome of miscarriage and complicated birth among women with rheumatoid arthritis (RA).

Methods: Data were extracted from health care databases of the Lombardy Region, Italy (2004-2013) as a part of the Record-Linkage on Rheumatic Diseases Study. Analyses included women with RA identified through a copayment exemption code (International Classification of Diseases, Ninth Revision, Clinical Modification code 714.

Side Effects of Curcumin: Epigenetic and Antiproliferative Implications for Normal Dermal Fibroblast and Breast Cancer Cells.

Background: Curcumin is a yellow-orange pigment obtained from the plant , which is known to exert beneficial effects in several diseases, including cancer. However, at high doses, it may produce toxic and carcinogenic effects in normal cells. In this context, we studied the effects of curcumin on normal human dermal fibroblast (HDF) cells and breast cancer cells (MCF7).

A Spectroscopic Study on Secondary Structure and Thermal Unfolding of the Plant Toxin Gelonin Confirms Some Typical Structural Characteristics and Unravels the Sequence of Thermal Unfolding Events.

Gelonin from the Indian plant belongs to the type I ribosome-inactivating proteins (RIPs). Like other members of RIPs, this toxin glycoprotein inhibits protein synthesis of eukaryotic cells; hence, it is largely used in the construction of immunotoxins composed of cell-targeted antibodies. Lysosomal degradation is one of the main issues in targeted tumor therapies, especially for type I RIP-based toxins, as they lack the translocation domains.

Booster Vaccination With GVGH 1790GAHB GMMA Vaccine Compared to Single Vaccination in Unvaccinated Healthy European Adults: Results From a Phase 1 Clinical Trial.

The investigational vaccine (1790GAHB) based on GMMA (generalized modules for membrane antigens) is immunogenic, with an acceptable safety profile in adults. However, pre-vaccination anti- lipopolysaccharide (LPS) antibody levels seemed to impact vaccine-related immune responses. This phase 1, open-label, non-randomized extension study (ClinicalTrials.

Glutathione compartmentalization and its role in glutathionylation and other regulatory processes of cellular pathways.

Glutathione is considered the major non-protein low molecular weight modulator of redox processes and the most important thiol reducing agent of the cell. The biosynthesis of glutathione occurs in the cytosol from its constituent amino acids, but this tripeptide is also present in the most important cellular districts, such as mitochondria, nucleus, and endoplasmic reticulum, thus playing a central role in several metabolic pathways and cytoprotection mechanisms. Indeed, glutathione is involved in the modulation of various cellular processes and, not by chance, it is a ubiquitous determinant for redox signaling, xenobiotic detoxification, and regulation of cell cycle and death programs.

Interaction of γ-conglutin from Lupinus albus with model phospholipid membranes: Investigations on structure, thermal stability and oligomerization status.

Interaction with model phospholipid membranes of lupin seed γ-conglutin, a glycaemia-lowering protein from Lupinus albus seeds, has been studied by means of Fourier-Transform infrared spectroscopy at pH 7.0 and at pH 4.5.

Protein-protein interactions of human glyoxalase II: findings of a reliable docking protocol.

Glyoxalase II (GlxII) is an antioxidant glutathione-dependent enzyme, which catalyzes the hydrolysis of S-d-lactoylglutathione to form d-lactic acid and glutathione (GSH). The last product is the most important thiol reducing agent present in all eukaryotic cells that have mitochondria and chloroplasts. It is generally known that GSH plays a crucial role not only in the cellular redox state but also in various cellular processes.

A Phase 2a Randomized Study to Evaluate the Safety and Immunogenicity of the 1790GAHB Generalized Modules for Membrane Antigen Vaccine against Administered Intramuscularly to Adults from a Shigellosis-Endemic Country.

Shigellosis is a mild-to-severe diarrheal infection, caused by the genus , and is responsible for significant morbidity and mortality worldwide. We evaluated the safety and immunogenicity of an investigational vaccine (1790GAHB) based on generalized modules for membrane antigens (GMMA) in Kenya, a -endemic country. This phase 2a, observer-blind, controlled randomized study (NCT02676895) enrolled 74 healthy adults aged 18-45 years, of whom 72 were vaccinated.

Self-organization in a diversity induced thermodynamics.

In this work we show how global self-organized patterns can come out of a disordered ensemble of point oscillators, as a result of a deterministic, and not of a random, cooperative process. The resulting system dynamics has many characteristics of classical thermodynamics. To this end, a modified Kuramoto model is introduced, by including Euclidean degrees of freedom and particle polarity.

Safety Profile and Immunologic Responses of a Novel Vaccine Against Shigella sonnei Administered Intramuscularly, Intradermally and Intranasally: Results From Two Parallel Randomized Phase 1 Clinical Studies in Healthy Adult Volunteers in Europe.

Background: Approximately 164,000 deaths yearly are due to shigellosis, primarily in developing countries. Thus, a safe and affordable Shigella vaccine is an important public health priority. The GSK Vaccines Institute for Global Health (GVGH) developed a candidate Shigella sonnei vaccine (1790GAHB) using the Generalized Modules for Membrane Antigens (GMMA) technology.

A possible S-glutathionylation of specific proteins by glyoxalase II: An in vitro and in silico study.

Unlabelled: Glyoxalase II, the second of 2 enzymes in the glyoxalase system, is a hydroxyacylglutathione hydrolase that catalyses the hydrolysis of S-d-lactoylglutathione to form d-lactic acid and glutathione, which is released from the active site. The tripeptide glutathione is the major sulfhydryl antioxidant and has been shown to control several functions, including S-glutathionylation of proteins. S-Glutathionylation is a way for the cells to store reduced glutathione during oxidative stress, or to protect protein thiol groups from irreversible oxidation, and few enzymes involved in protein S-glutathionylation have been found to date.

Amyloid fibril formation by bovine α1-acid glycoprotein in a reducing environment: The role of disulfide bridges on the observed aggregation kinetics.

Bovine α1-acid glycoprotein (bAGP), a thermostable counterpart of its human homologue, is a positive acute phase protein involved in binding and transportation of a large number of bio-active molecules and drugs across the body. We have investigated the effect of low pH and reducing conditions on the structure of the protein and found that it aggregates at high temperatures. The aggregates show a fibrillar structure when observed with electron microscopy.

Allergic Rhinitis in Children: A Randomized Clinical Trial Targeted at Symptoms.

Allergic rhinitis (AR) underlies many symptoms and complications which severely affect children's quality of life. This two-arm study aimed at evaluate the efficacy and safety of the medical device Narivent(®) versus topical corticosteroids in the symptomatic management of allergic rhinitis in paediatric patients. A randomized study was conducted.

The thermal unfolding of the ribosome-inactivating protein saporin-S6 characterized by infrared spectroscopy.

Saporin-S6 is a plant toxin belonging to the type 1 ribosome-inactivating protein (RIP) family. Since it was extracted and isolated from Saponaria officinalis for the first time almost thirty years ago, the protein has been widely studied mainly for its potential applications in anti-tumour and anti-viral infection therapy. Like other RIPs, saporin-S6 is particularly effective in the form of immunotoxin conjugated with monoclonal antibodies and its chemico-physical characteristics made the protein a perfect candidate for the synthesis, development and use of saporin-S6-based chimeric toxins.

Analysis of the link between the redox state and enzymatic activity of the HtrA (DegP) protein from Escherichia coli.

Bacterial HtrAs are proteases engaged in extracytoplasmic activities during stressful conditions and pathogenesis. A model prokaryotic HtrA (HtrA/DegP from Escherichia coli) requires activation to cleave its substrates efficiently. In the inactive state of the enzyme, one of the regulatory loops, termed LA, forms inhibitory contacts in the area of the active center.