Genetic and biotechnological approaches to preserve food quality against climate change

In this past decade, the bond between agriculture, food security, and climate change has become increasingly strong. Agriculture is recognized as one of the most endangered systems adversely affected by human activities and environmental issues. In particular, abiotic stress limits the quantity and quality of plant-based food. Heat stress, drought, and salinity impact plants at all different life stages, inducing morphological and physiological changes and provoking a reduction in their nutritional value. Accordingly, low-quality food results in a serious risk for the health of people worldwide. In this scenario, different genetic and biotechnological strategies have been investigated, including the use of New Plant Breeding Techniques (NBTs) and plant cell cultures. In this review, we describe how abiotic stresses alter the property and availability of nutritious food. In addition, we illustrate the advanced techniques that could be employed to address these issues and ameliorate the agricultural practices

Immuno-Modulatory Properties of a Quinolin-2-(1H)-on-3-Carboxamide Derivative: Relevance in Multiple Sclerosis

Background: We have recently released the structure of a class of quinolin-2-(1H)-on-3-carboxamide derivatives and among them; the drug A2 has the highest CB2 receptor selectivity. Objective: In this work we assessed the immuno-modulatory properties of A2 in lymphocytes isolated from peripheral blood of multiple sclerosis patients and healthy donors. Methods: Cell proliferative response was measured by 3H-thymidine incorporation, cell viability and apoptosis by trypan blue, annexin V staining and western blot. Cell activation was investigated by flow cytometry and molecular pathways by western blot. Results: A2 exerted anti-proliferative effects with down-regulation of TNF-α , IL-10 and Rantes in both cell types. No relevant changes were observed in cell viability between the two cell types. In cells from healthy subjects, A2 did not induce apoptosis, inhibited the cell cycle and similarly down-regulated in CD4+T cells the markers CD69, CD25, CD49d and CD54. Indeed, A2 also inhibited the phosphorylation of Akt, NF-kB, IKKα/β, ERK and blocked the expression of Cox-2 and CB2 receptor. Published patents also describe CB2 receptor agonists like purine derivatives. Differently, in cells from patients, A2 did not affect CD49d, while potently blocked CD54 expression. A2 inhibitory effects of Akt and Cox-2 expression were confirmed, whereas unchanged level of the CB2 receptor was observed in these cells. Conclusion: We reported similar effects of A2 in both cell types; however, a different mechanism of action might be suggested in cells from patients concerning cell activation and CB2 receptor expression. Overall, these data suggest an anti-inflammatory profile of A2 with potential implication in multiple sclerosis

Glycogen Synthase Kinase 3: Ion Channels, Plasticity, and Diseases

Glycogen synthase kinase 3β (GSK3) is a multifaceted serine/threonine (S/T) kinase expressed in all eukaryotic cells. GSK3β is highly enriched in neurons in the central nervous system where it acts as a central hub for intracellular signaling downstream of receptors critical for neuronal function. Unlike other kinases, GSK3β is constitutively active, and its modulation mainly involves inhibition via upstream regulatory pathways rather than increased activation. Through an intricate converging signaling system, a fine-tuned balance of active and inactive GSK3β acts as a central point for the phosphorylation of numerous primed and unprimed substrates. Although the full range of molecular targets is still unknown, recent results show that voltage-gated ion channels are among the downstream targets of GSK3β. Here, we discuss the direct and indirect mechanisms by which GSK3β phosphorylates voltage-gated Na+ channels (Nav 1.2 and Nav 1.6) and voltage-gated K+ channels (Kv 4 and Kv 7) and their physiological effects on intrinsic excitability, neuronal plasticity, and behavior. We also present evidence for how unbalanced GSK3β activity can lead to maladaptive plasticity that ultimately renders neuronal circuitry more vulnerable, increasing the risk for developing neuropsy-chiatric disorders. In conclusion, GSK3β-dependent modulation of voltage-gated ion channels may serve as an important pharmacological target for neurotherapeutic development

Changes upon the gluten-free diet of HLA-DQ2 and TRAFD1 gene expression in peripheral blood of celiac disease patients

Background: Celiac disease (CD) is a chronic immuno-mediated enteropathy caused by dietary gluten in genetically susceptible individuals carrying HLA (Human Leukocytes Antigen) genes that encode for DQ2.5 and DQ8 molecules. TRAFD1 (TRAF-type zinc finger domain 1) is a gene recently found associated with CD and defined as a master regulator of IFNγ signalling and of MHC class I antigen processing/presentation. There is no specific drug therapy and the only effective treatment is the gluten-free diet (GFD). The great majority of celiac patients when compliant with GFD have a complete remission of symptoms and recovery of gut mucosa architecture and function. Until now, very few studies have investigated molecular differences occurring in CD patients upon the GFD therapy. Methods: We looked at the expression of both HLA DQ2.5 and TRAFD1 risk genes in adult patients with acute CD at the time of and in treated patients on GFD. Specifically, we measured by qPCR the HLA-DQ2.5 and TRAFD1 mRNAs on peripheral blood mononuclear cells (PBMC) from the two groups of patients. Results: When we compared the HLA-DQ mRNA expression, we didn't find significant variation between the two groups of patients, thus indicating that GFD patients have the same capability to present gliadin antigens to cognate T cells as patients with active disease. Conversely, TRAFD1 was more expressed in PBMC from treated CD subjects. Notably, TRAFD1 transcripts significantly increased in the patients analyzed longitudinally during the GFD, indicating a role in the downregulation of gluten-induced inflammatory pathways. Conclusion: Our study demonstrated that HLA-DQ2.5 and TRAFD1 molecules are two important mediators of anti-gluten immune response and inflammatory process

Lovastatin induces apoptosis of k-ras-transformed thyroid cells via inhibition of ras farnesylation and by modulating redox state.

Transformation of thyroid cells with either K-ras or H-ras viral oncogenes produces cell types with different phenotype and different response to the inhibition of the prenylation pathway by 3-hydroxy-3-methylglutaryl-CoA reductase or farnesyltransferase inhibitors. These inhibitors induce apoptosis in K-ras-transformed FRTL-5 cells (FRTL-5-K-Ras) whereas cell cycle arrest is induced in H-ras-transformed FRTL-5 (FRTL-5-H-Ras). In FRTL-5-K-Ras cells, the product of K-ras gene is implicated in the scavenging of reactive oxygen species (ROS) through the activation of extracellular-signal-regulated kinase (ERK)1/2 kinases. We observed that lovastatin blocked ras activation through inhibition of farnesylation and induced apoptosis, increasing ROS levels through inhibition of ERK1/2 signaling and Mn-SOD expression. Lovastatin-induced apoptosis was due to intracellular ROS increase since both, the antioxidant compound pyrrolidinedithiocarbamate or the SOD-mimetic compound, antagonized apoptosis. Moreover, both p38 mitogen-activated protein kinase and nuclear factor kappaB pathways, activated as a consequence of high ROS levels, are involved in the apoptotic effect, indicating that cell death induced by lovastatin was dependent on oxidative stress. Lovastatin antitumor efficacy in K-ras-dependent thyroid tumors was further confirmed in vivo, proposing a new therapeutic strategy for those tumor diseases that are sustained by an inappropriate K-ras expression

Seismic vulnerability assessment of existing Italian hospitals: The case study of the national cancer institute “G. Pascale foundation” of Naples

Introduction: A large portion of the Italian built heritage is characterized by a significant seismic vulnerability since many structures were designed with outdated criteria, i.e., without accounting for seismic actions. This aspect is particularly relevant for strategic structures and infrastructures, whose functionalities are crucial in case of seismic events. Objective: The main aim of the present paper is to share the key findings related to the seismic vulnerability assessment of the National Institute for the Study and Treatment of Cancer (IRCCS) “Giovanni Pascale Foundation” in Naples. In particular, the main evidences could be easily extended to existing hospitals realized in the last century, with the main reference to: construction techniques, quality of constructional material, overt and convert seismic vulnerabilities and possible intervention strategies for risk mitigation. Methods: In the present paper, the assessment methodologies adopted for such a strategic hospital complex are provided, focusing in particular on: i. preliminary research of original design documents and on-site investigation for determining constructional details; ii. material tests on structural elements; iii. vulnerability seismic assessment by means of non-linear FE analyses (push-over and capacity spectrum method); iv. recommendations on retrofitting measures and cost estimations. Results: The conducted study puts into clear evidence the inadequacy of the investigated buildings to face the design seismic actions provided by the current Italian code and thus showed the significant seismic vulnerabilities affecting the Institute “G. Pascale Foundation” of Naples. Among these, particular attention has also been focused on the so-called intrinsic vulnerabilities, namely the ones not measurable explicitly and interesting non-structural elements (e.g., connection of shelves, stained glass windows, facilities, etc.). Conclusion: The presented case study highlights the strong seismic vulnerability affecting structures realized in the past century, despite their strategic functions. On the whole, the examined structures can be considered as representative of this building typology, and the adopted calculation criteria, as well as the assumptions of the assessment process, could be easily extended to similar case studies