Impaired Leptin Signalling in Obesity: Is Leptin a New Thermolipokine?

Leptin is a principal adipose-derived hormone mostly implicated in the regulation of energy balance through the activation of anorexigenic neuronal pathways. Comprehensive studies have established that the maintenance of certain concentrations of circulating leptin is essential to avoid an imbalance in nutrient intake. Indeed, genetic modifications of the leptin/leptin receptor axis and the obesogenic environment may induce changes in leptin levels or action in a manner that accelerates metabolic dysfunctions, resulting in a hyperphagic status and adipose tissue expansion. As a result, a vicious cycle begins wherein hyperleptinaemia and leptin resistance occur, in turn leading to increased food intake and fat enlargement, which is followed by leptin overproduction. In addition, in the context of obesity, a defective thermoregulatory response is associated with impaired leptin signalling overall within the ventromedial nucleus of the hypothalamus. These recent findings highlight the role of leptin in the regulation of adaptive thermogenesis, thus suggesting leptin to be potentially considered as a new thermolipokine. This review provides new insight into the link between obesity, hyperleptinaemia, leptin resistance and leptin deficiency, focusing on the ability to restore leptin sensitiveness by way of enhanced thermogenic responses and highlighting novel anti-obesity therapeutic strategies.     

Correction to J Sci Food Agric 79, 476-480 (1999) in the paper ‘Ferulic and caffeic acids as potential protective agents against photooxidative skin damage’ by A. Saija et al.

Grants from EU project - OLITEXT FAIR 97-3053 and CNR FERS-PO-94/99 OEVOCAL are gratefully acknowledged.     

Endothelial Progenitor Cells: An Appraisal of Relevant Data from Bench to Bedside

The mobilization of endothelial progenitor cells (EPCs) into circulation from bone marrow is well known to be present in several clinical settings, including acute coronary syndrome, heart failure, diabetes and peripheral vascular disease. The aim of this review was to explore the current literature focusing on the great opportunity that EPCs can have in terms of regenerative medicine.     

How sensory sensitivity to graininess could be measured?

Considering the lack of the literature and the need for developing a valid method to measure the texture sensitivity, in this study, we investigated the individual sensitivity to discriminate among different levels of graininess. With this purpose, five samples of cocoa-based creams were prepared, by changing the refining time. Samples were first characterized in terms of particles size distribution, by means of laser diffraction. Then, 59 subjects evaluated the cream sample graininess intensity, by using gLM scales, and their liking, by using LAM scales. The graininess scores of each subject were fitted with a power model, already observed with the instrumental results, estimating both the power law exponent and the R² coefficient, and using them as clustering parameters. Subjects were then clustered into three groups: high sensitivity; moderate sensitivity; low sensitivity. First, as it was hypothesized, results showed a significant difference between the three groups in terms of perceived graininess. Second, even though results showed a significant difference between the three groups in terms of perceived graininess, only little differences were found in terms of liking scores. Indeed, all the samples were equally liked for both the moderate and low sensitivity groups, whereas a significant trend was observed for the highly sensitive subjects who liked more the most refined samples. No significant relationships were found with age, and only a little trend was observed with gender: females seemed to be more sensitive than males. Texture attributes discrimination ability, as for example sensitivity to graininess, could affect food rejection or preferences and choice, but it is poorly investigated. This exploratory study, proposes a method to cluster consumers, based on their sensitivity. A statistical methodology has been developed to discriminate among consumer sensitivity levels. The results provide useful information about graininess sensitivity suggesting that the used methodologies could be applied to other texture properties resulting in a valid tool for the industry in the development and optimization of tailored new products.     

Inflammatory Microenvironment and Specific T Cells in Myeloproliferative Neoplasms: Immunopathogenesis and Novel Immunotherapies

The Philadelphia-negative myeloproliferative neoplasms (MPNs) are malignancies of the hematopoietic stem cell (HSC) arising as a consequence of clonal proliferation driven by somatically acquired driver mutations in discrete genes (JAK2, CALR, MPL). In recent years, along with the advances in molecular characterization, the role of immune dysregulation has been achieving increasing relevance in the pathogenesis and evolution of MPNs. In particular, a growing number of studies have shown that MPNs are often associated with detrimental cytokine milieu, expansion of the monocyte/macrophage compartment and myeloid-derived suppressor cells, as well as altered functions of T cells, dendritic cells and NK cells. Moreover, akin to solid tumors and other hematological malignancies, MPNs are able to evade T cell immune surveillance by engaging the PD-1/PD-L1 axis, whose pharmacological blockade with checkpoint inhibitors can successfully restore effective antitumor responses. A further interesting cue is provided by the recent discovery of the high immunogenic potential of JAK2V617F and CALR exon 9 mutations, that could be harnessed as intriguing targets for innovative adoptive immunotherapies. This review focuses on the recent insights in the immunological dysfunctions contributing to the pathogenesis of MPNs and outlines the potential impact of related immunotherapeutic approaches.     

Homozygous HESX1 and COL1A1 Gene Variants in a Boy with Growth Hormone Deficiency and Early Onset Osteoporosis

We report on a patient born to consanguineous parents, presenting with Growth Hormone Deficiency (GHD) and osteoporosis. SNP-array analysis and exome sequencing disclosed long contiguous stretches of homozygosity and two distinct homozygous variants in HESX1 (Q6H) and COL1A1 (E1361K) genes. The HESX1 variant was described as causative in a few subjects with an incompletely penetrant dominant form of combined pituitary hormone deficiency (CPHD). The COL1A1 variant is rare, and so far it has never been found in a homozygous form. Segregation analysis showed that both variants were inherited from heterozygous unaffected parents. Present results further elucidate the inheritance pattern of HESX1 variants and recommend assessing the clinical impact of variants located in C-terminal propeptide of COL1A1 gene for their potential association with rare recessive and early onset forms of osteoporosis.     

Epigenetic Deregulation of MicroRNAs in Rhabdomyosarcoma and Neuroblastoma and Translational Perspectives

Gene expression control mediated by microRNAs and epigenetic remodeling of chromatin are interconnected processes often involved in feedback regulatory loops, which strictly guide proper tissue differentiation during embryonal development. Altered expression of microRNAs is one of the mechanisms leading to pathologic conditions, such as cancer. Several lines of evidence pointed to epigenetic alterations as responsible for aberrant microRNA expression in human cancers. Rhabdomyosarcoma and neuroblastoma are pediatric cancers derived from cells presenting features of skeletal muscle and neuronal precursors, respectively, blocked at different stages of differentiation. Consistently, tumor cells express tissue markers of origin but are unable to terminally differentiate. Several microRNAs playing a key role during tissue differentiation are often epigenetically downregulated in rhabdomyosarcoma and neuroblastoma and behave as tumor suppressors when re-expressed. Recently, inhibition of epigenetic modulators in adult tumors has provided encouraging results causing re-expression of anti-tumor master gene pathways. Thus, a similar approach could be used to correct the aberrant epigenetic regulation of microRNAs in rhabdomyosarcoma and neuroblastoma. The present review highlights the current insights on epigenetically deregulated microRNAs in rhabdomyosarcoma and neuroblastoma and their role in tumorigenesis and developmental pathways. The translational clinical implications and challenges regarding modulation of epigenetic chromatin remodeling/microRNAs interconnections are also discussed.     

Effect of Calcium on Acrylamide Level and Sensory Properties of Cookies

Thermal process contaminants including acrylamide and hydroxymethylfurfural have been an intensive area of research in recent years. The main pathway of acrylamide formation is linked to the Maillard reaction. The first step is the formation of Schiff base between the carbonyl and α-amino group of asparagine. Presence of cations partially or completely eliminates the formation of Schiff base. This study aimed to investigate the effects of calcium chloride and calcium lactate on acrylamide and hydroxymethylfurfural levels in cookies. The effects of calcium derivatives on the sensory properties of cookies were also investigated. A direct relationship was determined between the amount of calcium in recipe and acrylamide formed in cookies. Addition of 1.0% of Puracal Act 100 decreased acrylamide concentration of cookies from 128 ± 10 ng/g to 24 ± 4 ng/g. In the same time, hydroxymethylfurfural concentration increased from 2.0 ± 0.19 mg/kg to 3.3 ± 0.24 mg/kg by the addition of 1.0% of Puracal Act 100. The calcium derivatives had no effect on cookie diameter and thickness, but the surface colors were different. The use of calcium significantly increased the lightness (L*) parameter, but decreased the redness (a*; p < 0.05). The sensory properties of cookies in terms of sweetness, saltiness and bitterness were not significantly affected by the addition of calcium derivatives at dosages up to 0.5% (p > 0.05).     

Metal-filled carbon nanotubes as a novel class of photothermal nanomaterials

Metal-filled carbon nanotubes represent a novel class of photothermal nanomaterials: when illuminated by visible light they exhibit a strong enhancement of the temperature at the metal sites, due to the enhanced plasmonic light absorption at the metal surface, which behaves as a heat radiator. Potential applications include nanomedicine, heat-assisted magnetic recording, and light-activated thermal gradient-driven devices.