Summary of the “Electroweak and QCD Physics” session

Summary of the “Electroweak and QCD Physics” session: theoretical and experimental talks

Brain function monitoring during off-pump cardiac surgery: a case report

BACKGROUND: Early postoperative stroke is an adverse syndrome after coronary bypass surgery. This report focuses on overcoming of cerebral ischemia as a result of haemodynamic instability during heart enucleation in off-pump procedure. CASE PRESENTATION: A 67 year old male patient, Caucasian race, with a body mass index of 28, had a recent non-Q posterolateral myocardial infarction one month before and recurrent instable angina. His past history includes an uncontrolled hypertension, dyslipidemia, insulin dependent diabetes mellitus, epiaortic vessel stenosis. The patient was scheduled for an off-pump procedure and monitored with bilateral somatosensory evoked potentials, whose alteration signalled the decrement of the cardiac index during operation. The somatosensory evoked potentials appeared when the blood pressure was increased with a pharmacological treatment. CONCLUSION: During the off-pump coronary bypass surgery, a lower cardiac index, predisposes patients, with multiple stroke risk factors, to a reduction of the cerebral blood flow. Intraoperative somatosensory evoked potentials monitoring provides informations about the functional status of somatosensory cortex to reverse effects of brain ischemia

The sea urchin embryo: A model to study Alzheimer’s beta amyloid induced toxicity

Alzheimer’s disease (AD) is the most common form of dementia. The cause of AD is closely related to the accumulation of amyloid beta peptide in the neuritic plaques. The use of animal model systems represents a good strategy to elucidate the molecular mechanism behind the development of this pathology. Here we use the Paracentrotus lividus embryo to identify molecules and pathways that can be involved in the degenerative process. As a first step, we identified the presence of an antigen related to the human APP, called PlAPP. This antigen, after gastrula stage, is processed producing a polypeptide of about 10 kDa. By immunohistochemistry we localized the PlAPP antigen in some serotonin expressing cells. Similarly, after 48 or 96 h incubation, a recombinant b-amyloid peptide, rAb42, accumulates around the intestinal tube and oesophagus. In addition, incubation of sea urchin embryos with two different solutions rich in oligomers and fibrillar aggregates of rAb42 induce activation of apoptosis as detected by TUNEL assay. Moreover, we demonstrate that aggregates induce apoptosis by extrinsic pathway activation, whereas oligomers induce apoptosis both by extrinsic and intrinsic pathway activation. Utilizing an apoptotic inhibitor, caspases activation was offset and morphological damage rescued. Taken together all these observations suggest that the sea urchin may be a simple and suitable model to characterize the mechanism underlining the cytotoxicity of Ab42

Metformin increases APP expression and processing via oxidative stress, mitochondrial dysfunction and NF-κB activation: Use of insulin to attenuate metformin's effect

AbstractClinical and experimental biomedical studies have shown Type 2 diabetes mellitus (T2DM) to be a risk factor for the development of Alzheimer's disease (AD). This study demonstrates the effect of metformin, a therapeutic biguanide administered for T2DM therapy, on β-amyloid precursor protein (APP) metabolism in in vitro, ex vivo and in vivo models. Furthermore, the protective role of insulin against metformin is also demonstrated. In LAN5 neuroblastoma cells, metformin increases APP and presenilin levels, proteins involved in AD. Overexpression of APP and presenilin 1 (Pres 1) increases APP cleavage and intracellular accumulation of β-amyloid peptide (Aβ), which, in turn, promotes aggregation of Aβ. In the experimental conditions utilized the drug causes oxidative stress, mitochondrial damage, decrease of Hexokinase-II levels and cytochrome C release, all of which lead to cell death. Several changes in oxidative stress-related genes following metformin treatment were detected by PCR arrays specific for the oxidative stress pathway. These effects of metformin were found to be antagonized by the addition of insulin, which reduced Aβ levels, oxidative stress, mitochondrial dysfunction and cell death. Similarly, antioxidant molecules, such as ferulic acid and curcumin, are able to revert metformin's effect. Comparable results were obtained using peripheral blood mononuclear cells. Finally, the involvement of NF-κB transcription factor in regulating APP and Pres 1 expression was investigated. Upon metformin treatment, NF-κB is activated and translocates from the cytoplasm to the nucleus, where it induces increased APP and Pres 1 transcription. The use of Bay11-7085 inhibitor suppressed the effect of metformin on APP and Pres 1 expression

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

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

Pharmacological activation of SIRT6 triggers lethal autophagy in human cancer cells

Sirtuin 6 (SIRT6) is a member of the NAD+-dependent class III deacetylase sirtuin family, which plays a key role in cancer by controlling transcription, genome stability, telomere integrity, DNA repair, and autophagy. Here we analyzed the molecular and biological effects of UBCS039, the first synthetic SIRT6 activator. Our data demonstrated that UBCS039 induced a time-dependent activation of autophagy in several human tumor cell lines, as evaluated by increased content of the lipidated form of LC3B by western blot and of autophagosomal puncta by microscopy analysis of GFP-LC3. UBCS039-mediated activation of autophagy was strictly dependent on SIRT6 deacetylating activity since the catalytic mutant H133Y failed to activate autophagy. At the molecular level, SIRT6-mediated autophagy was triggered by an increase of ROS levels, which, in turn, resulted in the activation of the AMPK-ULK1-mTOR signaling pathway. Interestingly, antioxidants were able to completely counteract UBCS039-induced autophagy, suggesting that ROS burst had a key role in upstream events leading to autophagy commitment. Finally, sustained activation of SIRT6 resulted in autophagy-related cell death, a process that was markedly attenuated using either a pan caspases inhibitor (zVAD-fmk) or an autophagy inhibitor (CQ). Overall, our results identified UBCS039 as an efficient SIRT6 activator, thereby providing a proof of principle that modulation of the enzyme can influence therapeutic strategy by enhancing autophagy-dependent cell death