Network-based approaches to explore complex biological systems towards network medicine

Network medicine relies on different types of networks: from the molecular level of protein–protein interactions to gene regulatory network and correlation studies of gene expression. Among network approaches based on the analysis of the topological properties of protein–protein interaction (PPI) networks, we discuss the widespread DIAMOnD (disease module detection) algorithm. Starting from the assumption that PPI networks can be viewed as maps where diseases can be identified with localized perturbation within a specific neighborhood (i.e., disease modules), DIAMOnD performs a systematic analysis of the human PPI network to uncover new disease-associated genes by exploiting the connectivity significance instead of connection density. The past few years have witnessed the increasing interest in understanding the molecular mechanism of post-transcriptional regulation with a special emphasis on non-coding RNAs since they are emerging as key regulators of many cellular processes in both physiological and pathological states. Recent findings show that coding genes are not the only targets that microRNAs interact with. In fact, there is a pool of different RNAs—including long non-coding RNAs (lncRNAs) —competing with each other to attract microRNAs for interactions, thus acting as competing endogenous RNAs (ceRNAs). The framework of regulatory networks provides a powerful tool to gather new insights into ceRNA regulatory mechanisms. Here, we describe a data-driven model recently developed to explore the lncRNA-associated ceRNA activity in breast invasive carcinoma. On the other hand, a very promising example of the co-expression network is the one implemented by the software SWIM (switch miner), which combines topological properties of correlation networks with gene expression data in order to identify a small pool of genes—called switch genes—critically associated with drastic changes in cell phenotype. Here, we describe SWIM tool along with its applications to cancer research and compare its predictions with DIAMOnD disease genes

Comprehensive characterization of the cis-regulatory code responsible for the spatio-temporal expression of olSix3.2 in the developing medaka forebrain

A cluster of highly conserved non-coding sequences surrounding the Six3 gene were identified in fish genomes, and transgenesis in medaka fish demonstrates that these sequences have enhancer, silencer and silencer blocker activities that are differentially combined to control the distribution of Six3

Major channels involved in neuropsychiatric disorders and therapeutic perspectives

Voltage-gated ion channels are important mediators of physiological functions in the central nervous system. The cyclic activation of these channels influences neurotransmitter release, neuron excitability, gene transcription, and plasticity, providing distinct brain areas with unique physiological and pharmacological response. A growing body of data has implicated ion channels in the susceptibility or pathogenesis of psychiatric diseases. Indeed, population studies support the association of polymorphisms in calcium and potassium channels with the genetic risk for bipolar disorders (BPDs) or schizophrenia. Moreover, point mutations in calcium, sodium, and potassium channel genes have been identified in some childhood developmental disorders. Finally, antibodies against potassium channel complexes occur in a series of autoimmune psychiatric diseases. Here we report recent studies assessing the role of calcium, sodium, and potassium channels in BPD, schizophrenia, and autism spectrum disorders, and briefly summarize promising pharmacological strategies targeted on ion channels for the therapy of mental illness and related genetic tests

Creating value-added cereal-based baked products: marketplace offer, laboratory-designed goods, and revisited local products

In recent years, the growing interest in well-being and healthy lifestyle, the increasing awareness of the relationship between non-communicable diseases and unhealthy diet, as well as the increasing prevalence of food intolerances have boosted the production of an increasing number of novel goods in both gluten-containing and gluten-free products market. The overall objective of this thesis was to create cereal-based baked products with added value with respect to those currently available on the European market, satisfying the consumers’ needs in terms of both sensory acceptability and superior nutritional profile. The research project was divided into three different parts. In the first part of the work a market study was performed to get a realistic and detailed overview of the current bread-market supply in both gluten-containing and gluten-free products market, in order to obtain an overall quality picture of the available offer in this prioritised food industry area. The second part evaluated the impact of wheat flour replacement up to 45% (weight basis) by incorporation of nutrience-dense raw materials (ancient cereals, pseudocereals and legumes) in improving wheat bread quality. Specific objectives were: a) to explore the competences and exploit the suitability of non-breadmaking whole grains (such as teff, buckwheat and green pea flours) with unique nutritional components to be simultaneously included in mixed wheat matrices, to obtain novel and healthy fermented baked goods meeting the functional and sensory restrictions of viscoelastic breadmaking systems; b) to investigate the thermal transitions that occur during starch gelatinization and retrogradation in these multicomponent bread matrices baked at restricted water availability, c) to evaluate the impact of non-breadmaking whole grains in the transition phases, and d) to explore the relationships between thermal properties and starch digestibility and firming kinetics of these multigrain bread matrices. The third part evaluated the impact of different flours, starches, polymeric substances, and surfactants on gluten-free dough performance to achieve gluten-free flat breads. The specific objective was to explore the capability of different gluten-free basic formulations made of different flour (rice, amaranth and chickpea) and starch (corn and cassava) blends, to make processable and viscoelastic GF-doughs in absence/presence of single hydrocolloids (guar gam, locust bean and psyllium fibre), proteins (milk and egg white) and surfactant (vegetable oil) in order to select the most promising formulations for producing the so called Spianata, a typical and widely consumed Sardinian flat bread

Techno-functional and nutritional performance of commercial breads available in Europe

In recent years, the growing interest for well-being and healthy lifestyle together with an increasing awareness of the close relationship between food and health have boosted the production of an increasing number of novel goods to be placed in both gluten-containing and gluten-free products market. The objective of this study was to provide a realistic and detailed overview of the current bread-market supply in order to evaluate the overall quality of the available offer in this prioritized food industry area. Twenty commercial breads consisting of gluten (n = 10) and gluten-free (n = 10) samples currently available in the European market have been assessed by physical-chemical, technological, nutritional, and sensory determinations. The quality parameters obtained were related to each other by using Pearson correlations, while sample classification was achieved by applying factor analysis. Higher values for protein and bio-accessible polyphenols content, aroma and taste quality, and low and moderate expected glycaemic index corresponded to gluten containing breads. Although the main distinction was between gluten and gluten-free samples as it was expected, classification of breads allowed differentiating samples with different formulations in terms of presence/absence of alternative, innovative, and nutrient-dense raw materials.Financial support of the Spanish institutions Consejo Superior de Investigaciones Científicas (CSIC) and Ministerio de Economía y Competitividad (Projects AGL2011-22669 and AGL2015-63849-C2-1-R). Paola Conte gratefully acknowledges Sardinia Regional Government for the financial support of her PhD scholarship (P.O.R. Sardegna F.S.E. Operational Programme of the Autonomous Region of Sardinia, European Social Fund 2007-2013 – Axis IV Human Resources, Objective l.3, Line of Activity l.3.1.).Peer reviewe

Gluten-free dough-making of specialty breads: Significance of blended starches, flours and additives on dough behaviour

The capability of different gluten-free (GF) basic formulations made of flour (rice, amaranth and chickpea) and starch (corn and cassava) blends, to make machinable and viscoelastic GF-doughs in absence/presence of single hydrocolloids (guar gum, locust bean and psyllium fibre), proteins (milk and egg white) and surfactants (neutral, anionic and vegetable oil) have been investigated. Macroscopic (high deformation) and macromolecular (small deformation) mechanical, viscometric (gelatinization, pasting, gelling) and thermal (gelatinization, melting, retrogradation) approaches were performed on the different matrices in order to (a) identify similarities and differences in GF-doughs in terms of a small number of rheological and thermal analytical parameters according to the formulations and (b) to assess single and interactive effects of basic ingredients and additives on GF-dough performance to achieve GF-flat breads. Larger values for the static and dynamic mechanical characteristics and higher viscometric profiles during both cooking and cooling corresponded to doughs formulated with guar gum and Psyllium fibre added to rice flour/starch and rice flour/corn starch/chickpea flour, while surfactant- and protein-formulated GF-doughs added to rice flour/starch/amaranth flour based GF-doughs exhibited intermediate and lower values for the mechanical parameters and poorer viscometric profiles. In addition, additive-free formulations exhibited higher values for the temperature of both gelatinization and retrogradation and lower enthalpies for the thermal transitions. Single addition of 10% of either chickpea flour or amaranth flour to rice flour/starch blends provided a large GF-dough hardening effect in presence of corn starch and an intermediate effect in presence of cassava starch (chickpea), and an intermediate reinforcement of GF-dough regardless the source of starch (amaranth). At macromolecular level, both chickpea and amaranth flours, singly added, determined higher values of the storage modulus, being strengthening effects more pronounced in presence of corn starch and cassava starch, respectively.The authors acknowledge the financial support of Regione Autonoma della Sardegna, Legge 7, project title “Ottimizzazione della formulazione e della tecnologia di processo per la produzione di prodotti da forno gluten-free fermentati e non fermentati” and Spanish institutions Consejo Superior de Investigaciones Científicas (CSIC) and Ministerio de Economía y Competitividad (Project AGL2011-22669).Peer Reviewe

Impact of ancient cereals, pseudocereals and legumes on starch hydrolysis and antiradical activity of technologically viable blended breads

Wheat flour replacement from 22.5% up to 45% by incorporation of ternary blends of teff (T), green pea (GP) and buckwheat (BW) flours provided technologically viable and acceptable sensory rated multigrain breads with superior nutritional value compared to the 100% wheat flour (WT) counterparts. Blended breads exhibited superior nutritional composition, larger amounts of bioaccessible polyphenols, higher anti-radical activity, and lower and slower starch digestibility. Simultaneous lower rapidly digestible starch (57.1%) and higher slowly digestible starch (12.9%) and resistant starch (2.8%) contents (g per 100 g fresh bread), considered suitable nutritional trends for dietary starch fractions, were met by the blend formulated 7.5% T, 15% GP, 15% BK. The associated mixture that replaced 37.5% WT, showed a rather lower extent and slower rate of starch hydrolysis with medium-low values for C, and H 90, and lowest k, and intermediate expected Glycaemic Index (86). All multigrain breads can be labelled as source of dietary fibre (¿3 g dietary fibre/100 g bread).The authors acknowledge the financial support of the Spanish institutions Consejo Superior de Investigaciones Científicas (CSIC) and Ministerio de Economía y Competitividad (Project AGL2011-22669).Peer Reviewe

SAveRUNNER: a network-based algorithm for drug repurposing and its application to COVID-19

The novelty of new human coronavirus COVID-19/SARS-CoV-2 and the lack of effective drugs and vaccines gave rise to a wide variety of strategies employed to fight this worldwide pandemic. Many of these strategies rely on the repositioning of existing drugs that could shorten the time and reduce the cost compared to de novo drug discovery. In this study, we presented a new network-based algorithm for drug repositioning, called SAveRUNNER (Searching off-lAbel dRUg aNd NEtwoRk), which predicts drug-disease associations by quantifying the interplay between the drug targets and the disease-specific proteins in the human interactome via a novel network-based similarity measure that prioritizes associations between drugs and diseases locating in the same network neighborhoods. Specifically, we applied SAveRUNNER on a panel of 14 selected diseases with a consolidated knowledge about their disease-causing genes and that have been found to be related to COVID-19 for genetic similarity, comorbidity, or for their association to drugs tentatively repurposed to treat COVID-19. Focusing specifically on SARS subnetwork, we identified 282 repurposable drugs, including some the most rumored off-label drugs for COVID-19 treatments, as well as a new combination therapy of 5 drugs, actually used in clinical practice. Furthermore, to maximize the efficiency of putative downstream validation experiments, we prioritized 24 potential anti-SARS-CoV repurposable drugs based on their network-based similarity values. These top-ranked drugs include ACE-inhibitors, monoclonal antibodies, and thrombin inhibitors. Finally, our findings were in-silico validated by performing a gene set enrichment analysis, which confirmed that most of the network-predicted repurposable drugs may have a potential treatment effect against human coronavirus infections.Comment: 42 pages, 9 figure

Bacterial biofilm associated with a case of capsular contracture

Capsular contracture is one of the most common complications of implant-based breast augmentation. Despite its prevalence, the etiology of capsular contracture remains controversial although the surface texture of the breast implant, the anatomical position of the prosthesis and the presence of bacterial biofilm could be considered trigger factors. In fact, all medical implants are susceptible to bacterial colonization and biofilm formation. The present study demonstrated the presence of microbial biofilm constituted by cocci in a breast implant obtained from a patient with Baker grade II capsular contracture. This suggests that subclinical infection can be present and involved in low-grade capsular contracture

imaging the kidney from light to super resolution microscopy

Abstract The important achievements in kidney physiological and pathophysiological mechanisms can largely be ascribed to progress in the technology of microscopy. Much of what we know about the architecture of the kidney is based on the fundamental descriptions of anatomic microscopists using light microscopy and later by ultrastructural analysis provided by electron microscopy. These two techniques were used for the first classification systems of kidney diseases and for their constant updates. More recently, a series of novel imaging techniques added the analysis in further dimensions of time and space. Confocal microscopy allowed us to sequentially visualize optical sections along the z-axis and the availability of specific analysis software provided a three-dimensional rendering of thicker tissue specimens. Multiphoton microscopy permitted us to simultaneously investigate kidney function and structure in real time. Fluorescence-lifetime imaging microscopy allowed to study the spatial distribution of metabolites. Super-resolution microscopy increased sensitivity and resolution up to nanoscale levels. With cryo-electron microscopy, researchers could visualize the individual biomolecules at atomic levels directly in the tissues and understand their interaction at subcellular levels. Finally, matrix-assisted laser desorption/ionization imaging mass spectrometry permitted the measuring of hundreds of different molecules at the same time on tissue sections at high resolution. This review provides an overview of available kidney imaging strategies, with a focus on the possible impact of the most recent technical improvements