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Bergamot flavonoids have been shown to prevent metabolic syndrome, non-alcoholic fatty liver disease (NAFLD) and stimulate autophagy in animal models and patients. To investigate further the mechanism of polyphenol-dependent effects, we performed a RT2-PCR array analysis on 168 metabolism, transport and autophagy-related genes expressed in rat livers exposed for 14 weeks to different diets: standard, cafeteria (CAF) and CAF diet supplemented with 50 mg/kg of bergamot polyphenol fraction (BPF). CAF diet caused a strong upregulation of gluconeogenesis pathway (Gck, Pck2) and a moderate (>1.7 fold) induction of genes regulating lipogenesis (Srebf1, Pparg, Xbp1), lipid and cholesterol transport or lipolysis (Fabp3, Apoa1, Lpl) and inflammation (Il6, Il10, Tnf). However, only one β-oxidation gene (Cpt1a) and a few autophagy genes were differentially expressed in CAF rats compared to controls. While most of these transcripts were significantly modulated by BPF, we observed a particularly potent effect on lipogenesis genes, like Acly, Acaca and Fasn, which were suppressed far below the mRNA levels of control livers as confirmed by alternative primers-based RT2-PCR analysis and western blotting. These effects were accompanied by downregulation of pro-inflammatory cytokines (Il6, Tnfa, and Il10) and diabetes-related genes. Few autophagy (Map1Lc3a, Dapk) and no β-oxidation gene expression changes were observed compared to CAF group. In conclusion, chronic BPF supplementation efficiently prevents NAFLD by modulating hepatic energy metabolism and inflammation gene expression programs, with no effect on β-oxidation, but profound suppression of de novo lipogenesis. [ABSTRACT FROM AUTHOR]

Anderson–Fabry disease (AFD) is an X-linked multisystemic disorder with a heterogeneous phenotype, resulting from deficiency of the lysosomal enzyme α-galactosidase A (α-Gal A) and leading to globotriaosylceramide systemic accumulation. Lysosomal storage is not the unique player in organ failure and different mechanisms could drive tissue damage, including endoplasmic reticulum (ER) stress and its related signaling pathway's activation. We identified a new missense variant in the signal peptide of α-GLA gene, c.13 A/G, in a 55-year-old woman affected by chronic kidney disease, acroparesthesia, hypohidrosis, and deafness and exhibiting normal values of lysoGb3 and αGLA activity. The functional study of the new variant performed by its overexpression in HEK293T cells showed an increased protein expression of a key ER stress marker, GRP78, the pro-apoptotic BAX, the negative regulator of cell cycle p21, the pro-inflammatory cytokine, IL1β, together with pNFkB, and the pro-fibrotic marker, N-cadherin. Transmission electron microscopy showed signs of ER injury and intra-lysosomal inclusions. The proband's PBMC exhibited higher expression of TGFβ 1 and pNFkB compared to control. Our findings suggest that the new variant, although it did not affect enzymatic activity, could cause cellular damage by affecting ER homeostasis and promoting apoptosis, inflammation, and fibrosis. Further studies are needed to demonstrate the variant's contribution to cellular and tissue damage. [ABSTRACT FROM AUTHOR]

Alpha-lipoic acid (ALA) is a natural antioxidant dithiol compound, exerting antiproliferative and antimetastatic effects in various cancer cell lines. In our study, we demonstrated that ALA reduces the cell growth of prostate cancer cells LNCaP and DU-145. Western blot results revealed that in both cancer cells, ALA, by upregulating pmTOR expression, reduced the protein content of two autophagy initiation markers, Beclin-1 and MAPLC3. Concomitantly, MTT assays showed that chloroquine (CQ) exposure, a well-known autophagy inhibitor, reduced cells' viability. This was more evident for treatment using the combination ALA + CQ, suggesting that ALA can reduce cells' viability by inhibiting autophagy. In addition, in DU-145 cells we observed that ALA affected the oxidative/redox balance system by deregulating the KEAP1/Nrf2/p62 signaling pathway. ALA decreased ROS production, SOD1 and GSTP1 protein expression, and significantly reduced the cytosolic and nuclear content of the transcription factor Nrf2, concomitantly downregulating p62, suggesting that ALA disrupted p62-Nrf2 feedback loop. Conversely, in LNCaP cells, ALA exposure upregulated both SOD1 and p62 protein expression, but did not affect the KEAP1/Nrf2/p62 signaling pathway. In addition, wound-healing, Western blot, and immunofluorescence assays evidenced that ALA significantly reduced the motility of LNCaP and DU-145 cells and downregulated the protein expression of TGFβ1 and vimentin and the deposition of fibronectin. Finally, a soft agar assay revealed that ALA decreased the colony formation of both the prostate cancer cells by affecting the anchorage independent growth. Collectively, our in vitro evidence demonstrated that in prostate cancer cells, ALA reduces cell growth and counteracts both migration and invasion. Further studies are needed in order to achieve a better understanding of the underlined molecular mechanisms. [ABSTRACT FROM AUTHOR]

Objectives: Natural products are valuable sources of nutraceuticals for the prevention or treatment of ischemic stroke, a major cause of death and severe disability worldwide. Among the mechanisms implicated in cerebral ischemia-reperfusion damage, oxidative stress exerts a pivotal role in disease progression. Given the high antioxidant potential of most components of sunflower oil, we have explored its effects on ischemic brain injury produced in the mouse by transient occlusion of the middle cerebral artery (MCAo). Key findings: Intraperitoneal (i.p.) administration of sunflower oil at doses of 3 ml/kg (48 h, 24 h and 1 h before MCAo) significantly reduced brain infarct volume and oedema assessed 24 h after the insult. This neuroprotective treatment schedule also prevented the elevation of brain lipid peroxidation produced by MCAo-reperfusion injury. By contrast, doses of 0.03 ml/kg of sunflower oil resulted ineffective on both cerebral damage and lipid peroxidation. Although sunflower oil did not affect serum levels of Diacron-reactive oxygen metabolites (d-ROMs), both 0.03 and 3 ml/kg dosing regimens resulted in the preservation of serum biological antioxidant potential (BAP) that was otherwise dramatically reduced 24 h after MCAo. Conclusions: Sunflower oil represents a promising source of neuroprotective extracts/compounds that can be exploited for the prevention and/or treatment of cerebral ischemia. [ABSTRACT FROM AUTHOR]

This paper deals with the formulation of innovative mortars for the consolidation of archeological structures in underwater environment. The research was conducted within the frame of the MaTaCoS project (Advanced materials and technologies applied to the conservation of underwater cultural heritage) funded by MISE (Italian Ministry of Economic Development). The project concerns the design of advanced tools and methods for the protection of Underwater Cultural Heritage, through specific cleaning and consolidating procedures to be applied directly in situ. The fishpond of the archaeological site of Castrum Novum (Santa Marinella, Rome, Italy) was chosen as a pilot site for experimentation. It is a structure on the coastline, composed of only one tank, with an average immersion of 0.37 m below the sea level, and developing with an NE/SW orientation. The masonry structures reach the maximum thickness at the apex of the fishpond (4.70 m) and consist of a concrete conglomerate composed of slightly rough stones of medium size bound with non-hydraulic mortar. Selected mortars' fragments taken from the fishpond were characterized by means of minero-petrographic technique in order to define their main constituents from a compositional and textural point of view and also to identify the various degradation processes, mainly biological colonization. Starting from the acquired information, innovative mortars were formulated with the addition of two different anti-fouling additives aimed to slow down the above-mentioned degradation. The efficacy of the anti-fouling products was tested on specimens settled in laboratory environment (artificial marine environment). This information could be useful both for the definition of restoration interventions and for planning preservation protocols to be applied in this peculiar environment. [ABSTRACT FROM AUTHOR]

Aim: Centenarians represent a biological model of successful aging because they escaped/postponed most invalidating age‐related diseases, such as cardiovascular diseases. The aim of the present study was to clarify whether a favorable cardiovascular risk profile increases the survival chances in long‐lived people. Methods: A total of 355 community‐dwelling nonagenarians and centenarians living in Southern Italy were recruited in the study. Patients were classified as at low and high cardiovascular risk on the basis of serum cholesterol, diabetes, hypertension and smoking status. The relationship between cardiovascular risk factors and 10‐year mortality was investigated by Cox regression analysis. Splines‐based hazard ratio curves were also estimated for total cholesterol, low‐density lipoprotein cholesterol, and systolic and diastolic blood pressure. Results: Low levels of selected cardiovascular risk factors usually associated with lower mortality in adults do not increase survival chances among oldest‐old individuals. In particular, after adjusting for age, sex, and cognitive, functional and nutritional status, serum cholesterol >200 mg/dL increased the survival chances during the follow‐up period (hazard ratio 0.742, 95% CI 0.572–0.963). Conclusions: The present results showed that in nonagenarians and centenarians, the clinical and prognostic meaning associated with traditional cardiovascular risk factors is very different from younger populations. Consequently, considering the increase of this population segment, further studies are required to confirm these results and to translate them into clinical practice/primary care. Geriatr Gerontol Int 2019; 19: 165–170. [ABSTRACT FROM AUTHOR]

Obesity is a potent risk factor for kidney disease as it increases the possibility of developing diabetes and hypertension, and it has a direct impact on the development of chronic kidney disease and end-stage renal disease. In this study, we tested the effect of bergamot polyphenolic fraction in a cafeteria with diet-fed rats, an excellent experimental model for studying human metabolic syndrome, as it is able to induce severe obesity with insulin resistance and high plasma triglyceride levels more efficiently than a traditional lard-based high-fat diet used in rodent models. We analyzed the plasmatic oxidative balance by photometric tests, and the expression of cytoplasmic antioxidant enzymes (superoxide dismutase 1 and glutatione S-tranferasi P1) and apoptotic markers (Caspase 8 and 9) in kidney tissues by Western blot analysis. Our results clearly showed that the cafeteria diet induces a marked pro-oxidant effect: significant reduction of plasmatic antioxidant capacity; downregulation of cytoplasmic antioxidant enzymes expression; and activation of apoptotic pathways. All these hallmarks of redox disequilibrium were mitigated by treatment with polyphenolic fraction of bergamot, highlighting its antioxidant effect in the metabolic syndrome. Our data show that the link between obesity and renal damage could be represented by oxidative stress. [ABSTRACT FROM AUTHOR]