Insulin Resistance: A Bridge between T2DM and Alzheimer's Disease

T2DM is caused by insulin resistance in the tissues, no longer able to respond to the hormone action. It is most frequently associated with aging, a family history of diabetes, obesity, and failure of exercise.The insulin, ahormone produced by the beta-cells of the pancreas, is the key biomolecule for the regulation of carbohydrate and lipid metabolism. Although its action in body organs mainly concerns the glucose homeostasis, in Central Nervous System insulin performs several functions such as regulation of glucose metabolism, food intake and body weight, fertility and reproduction [1] and others not yet completely known. In particular, the high density of insulin receptors in the hippocampus and cerebral cortex regions has suggested its participation in learning and memory process. The administration of insulin to both humans and animal models has induced an enhancement of the memory function [2] and the treatment with insulin has given in several animal models beneficial effects to prevent memory loss after ischemia episodes whereas no effects are observed with glucose alone [3]. Insulin is also involved in the synaptic plasticity, for example, it as been show that insulin allows the long-lasting enhancement of GABA receptormediated synaptic transmission [4] and promote the internalization of AMPA receptors from the neuron synaptic membrane causing a long-term depression (LTD) of excitatory synaptic transmission in the hippocampus and cerebellum [5,6]. LTD is a process that, together with the opposite one, long-term potentiation has a great relevance for brain information storage and improvement of neurons links during development [7]. Furthermore, insulin receptor signaling regulates the maintenance of synapses and contributes to experience-dependent structural plasticity that is necessary for the recruitment of neurons into brain circuits [8]. Moreover, some studies suggest that insulin participates in neuronal differentiation of postnatal neural stem cell [9] and their culturing with both insulin and insulin-like growth factor (GF-1) causes a greater production of neurons during differentiation compared to culturesstimulated by IGF-1 alone [10]. Insulin also avoids the necrosis of rat embryonic neurons cultured in a serum-free medium; in fact the protein was capable to restore the cell viability by activation of Protein Kinase C, having the crucial role of controlling other proteins through the phosphorylation of their serine and threonine amino acid residues; on the contrary, insulinlike growth factor addition had no effect [11]. Clearly, in the insulin resistance state, these functions are impaired

Autophagy and rheumatoid arthritis: Current knowledges and future perspectives

Autophagy is a degradation mechanism by which cells recycle cytoplasmic components to generate energy. By influencing lymphocyte development, survival, and proliferation, autophagy regulates the immune responses against self and non-self antigens. Deregulation of autophagic pathway has recently been implicated in the pathogenesis of several autoimmune diseases, including rheumatoid arthritis (RA). Indeed, autophagy seems to be involved in the generation of citrullinated peptides, and also in apoptosis resistance in RA. In this review, we summarize the current knowledge on the role of autophagy in RA and discuss the possibility of a clinical application of autophagy modulation in this disease

How water-soluble saccharides drive the metabolism of lactic acid bacteria during fermentation of brewers' spent grain

We proposed a novel phenomic approach to track the effect of short-term exposures of Lactiplantibacillus plantarum and Leuconostoc pseudomesenteroides to environmental pressure induced by brewers' spent grain (BSG)-derived saccharides. Water-soluble BSG-based medium (WS-BSG) was chosen as model system. The environmental pressure exerted by WS-BSG shifted the phenotypes of bacteria in species- and strains-dependent way. The metabolic drift was growth phase-dependent and likely underlay the diauxic profile of organic acids production by bacteria in response to the low availability of energy sources. Among pentosans, metabolism of arabinose was preferred by L. plantarum and xylose by Leuc. pseudomesenteroides as confirmed by the overexpression of related genes. Bayesian variance analysis showed that phenotype switching towards galactose metabolism suffered the greatest fluctuation in L. plantarum. All lactic acid bacteria strains utilized more intensively sucrose and its plant-derived isomers. Sucrose-6-phosphate activity in Leuc. pseudomesenteroides likely mediated the increased consumption of raffinose. The increased levels of some phenolic compounds suggested the involvement of 6-phospho-beta-glucosidases in beta-glucosides degradation. Expression of genes encoding beta-glucoside/cellobiose-specific EII complexes and phenotyping highlighted an increased metabolism for cellobiose. Our reconstructed metabolic network will improve the understanding of how lactic acid bacteria may transform BSG into suitable food ingredients.Peer reviewe

Oxidative responsiveness to multiple stressors in the key Antarctic species, Adamussium colbecki: interactions between temperature, acidification and cadmium exposure.

Abstract: High-latitude marine ecosystems are ranked to be among the most sensitive regions to climate change since highly stenothermal and specially adapted organisms might be seriously affected by global warming and ocean acidification. The present investigation was aimed to provide new insights on the sensitivity to such environmental stressors in the key Antarctic species, Adamussium colbecki, focussing also on their synergistic effects with cadmium exposure, naturally abundant in this area for upwelling phenomena. Scallops were exposed for 2 weeks to various combinations of Cd (0 and 40 μgL-1), pH (8.05 and 7.60) and temperature (-1 and +1°C). Beside Cd bioaccumulation, a wide panel of early warning biomarkers were analysed in digestive glands and gills including levels of metallothioneins, individual antioxidants and total oxyradical scavenging capacity, onset of oxidative cell damage like lipid peroxidation, lysosomal stability, DNA integrity and peroxisomal proliferation. Results indicated reciprocal interactions between multiple stressors and their elaboration by a quantitative hazard model based on the relevance and magnitude of effects, highlighted a different sensitivity of analysed tissues. Due to cellular adaptations to high basal Cd content, digestive gland appeared more tolerant toward other prooxidant stressors, but sensitive to variations of the metal. On the other hand, gills were more affected by various combinations of stressors occurring at higher temperatur

Data concerning the proteolytic resistance and oxidative stress in LAN5 cells after treatment with BSA hydrogels

AbstractProteolytic resistance is a relevant aspect to be tested in the formulation of new nanoscale biomaterials. The action of proteolytic enzymes is a very fast process occurring in the range of few minutes. Here, we report data concerning the proteolytic resistance of a heat-set BSA hydrogel obtained after 20-hour incubation at 60°C prepared at the pH value of 3.9, pH at which the hydrogel presents the highest elastic character with respect to gel formed at pH 5.9 and 7.4 “Heat-and pH-induced BSA conformational changes, hydrogel formation and application as 3D cell scaffold” (G. Navarra, C. Peres, M. Contardi, P. Picone, P.L. San Biagio, M. Di Carlo, D. Giacomazza, V. Militello, 2016) [1]. We show that the BSA hydrogel produced by heating treatment is protected by the action of proteinase K enzyme. Moreover, we show that LAN5 cells cultured in presence of BSA hydrogels formed at pH 3.9, 5.9 and 7.4 did not exhibit any oxidative stress, one of the first and crucial events causing cell death “Are oxidative stress and mitochondrial dysfunction the key players in the neurodegenerative diseases?” (M. Di Carlo, D. Giacomazza, P. Picone, D. Nuzzo, P.L. San Biagio, 2012) [2] “Effect of zinc oxide nanomaterials induced oxidative stress on the p53 pathway” (M.I. Setyawati, C.Y. Tay, D.T. Leaong, 2013) [3]

Aphanizomenon flos-aquae (AFA) Extract Prevents Neurodegeneration in the HFD Mouse Model by Modulating Astrocytes and Microglia Activation

Obesity and related metabolic dysfunctions are associated with neurodegenerative diseases, such as Alzheimer's disease. Aphanizomenon flos-aquae (AFA) is a cyanobacterium considered a suitable supplement for its nutritional profile and beneficial properties. The potential neuroprotective effect of an AFA extract, commercialized as KlamExtra®, including the two AFA extracts Klamin® and AphaMax®, in High-Fat Diet (HFD)-fed mice was explored. Three groups of mice were provided with a standard diet (Lean), HFD or HFD supplemented with AFA extract (HFD + AFA) for 28 weeks. Metabolic parameters, brain insulin resistance, expression of apoptosis biomarkers, modulation of astrocytes and microglia activation markers, and Aβ deposition were analyzed and compared in the brains of different groups. AFA extract treatment attenuated HFD-induced neurodegeneration by reducing insulin resistance and loss of neurons. AFA supplementation improved the expression of synaptic proteins and reduced the HFD-induced astrocytes and microglia activation, and Aβ plaques accumulation. Together, these outcomes indicate that regular intake of AFA extract could benefit the metabolic and neuronal dysfunction caused by HFD, decreasing neuroinflammation and promoting Aβ plaques clearanc

A New Frontier of Photocatalysis Employing Micro-Sized TiO2: Air/Water Pollution Abatement and Self-Cleaning/ Antibacterial Applications

This chapter presents the use of a commercial micro-sized TiO2 powder as an alternative to the traditional nano-powders as semiconductors in photocatalytic processes. Results of the photocatalytic efficiency towards the photodegradation of the traditional pollutant molecules both in gas phase (nitrogen oxides (NOx) and volatile organic compounds (VOCs)) and in water phase (phenol) are presented and compared to the results obtained with two nano-sized reference powders. Micro-sized TiO2 is also industrially coated at the surfaces of porcelain grés tiles (Active Clean Air and Antibacterial Ceramic™). The possibility to have a photocatalytic material, strongly stuck at the surface of a vitrified tile, increases the use of photocatalysis in real conditions: no problem of filtration of the semiconductor from the liquid medium after use and no risks of leakage of nanoparticles in the atmosphere. Tests were performed using reactors equipped with UV-A lamps and with suitable analytical systems, depending on the final purpose. Characterization data from both powders and coated tiles are put in correlation with the photocatalytic results to understand the semiconductor action during the photocatalytic process. Polluting molecules were chosen in order to cover all the common aspects of environmental pollution: NOx and some VOCs represent the model molecules to test the efficiency of the micro-sized TiO2 (degradation from the pristine molecule to CO2 or inorganic salts) in gas phase. As for the water pollution, phenol was chosen as common pollutant in worldwide rivers. Moreover, tests on self-cleaning and antibacterial properties are also reported. The positive results of micro-sized TiO2 both in powder and coated onto the surface of porcelain grés tiles open the way to new photocatalytic products that do not make use of nanoscale powders avoiding problems to human safety caused by the inherent toxicity of the nanoparticles

Seawi—a sea urchin piwi/argonaute family member is a component of MT-RNP complexes

This is the publisher's version, also available electronically from http://rnajournal.cshlp.org/content/11/5/646.The piwi/argonaute family of proteins is involved in key developmental processes such as stem cell maintenance and axis specification through molecular mechanisms that may involve RNA silencing. Here we report on the cloning and characterization of the sea urchin piwi/argonaute family member seawi. Seawi is a major component of microtubule-ribonucleoprotein (MT-RNP) complexes isolated from two different species of sea urchin, Strongylocentrotus purpuratus and Paracentrotus lividus. Seawi co-isolates with purified ribosomes, cosediments with 80S ribosomes in sucrose density gradients, and binds microtubules. Seawi possesses the RNA binding motif common to piwi family members and binds P. lividus bep4 mRNA, a transcript that co-isolates with MT-RNP complexes and whose translation product has been shown to play a role in patterning the animal–vegetal axis. Indirect immunofluorescence studies localized seawi to the cortex of unfertilized eggs within granule-like particles, the mitotic spindle during cell division, and the small micromeres where its levels were enriched during the early cleavage stage. Lastly, we discuss how seawi, as a piwi/argonaute family member, may play a fundamentally important role in sea urchin animal–vegetal axis formation and stem cell maintenance