Transcriptomics and metabolomics integration reveals redox-dependent metabolic rewiring in breast cancer cells

Rewiring glucose metabolism toward aerobic glycolysis provides cancer cells with a rapid generation of pyruvate, ATP, and NADH, while pyruvate oxidation to lactate guarantees refueling of oxidized NAD+ to sustain glycolysis. CtPB2, an NADH-dependent transcriptional co-regulator, has been proposed to work as an NADH sensor, linking metabolism to epigenetic transcriptional reprogramming. By integrating metabolomics and transcriptomics in a triple-negative human breast cancer cell line, we show that genetic and pharmacological down-regulation of CtBP2 strongly reduces cell proliferation by modulating the redox balance, nucleotide synthesis, ROS generation, and scavenging. Our data highlight the critical role of NADH in controlling the oncogene-dependent crosstalk between metabolism and the epigenetically mediated transcriptional program that sustains energetic and anabolic demands in cancer cells

Primary antiphosholipid syndrome and hyperomocysteinemia: a study of a group of 29 patients

Objective. In order to investigate the potential role of hyperhomocysteinemia as an additional risk factor for thrombotic events, we studied its prevalence in patients with primary antiphospholipid syndrome (APS) and evaluated its association with different clinical features. Methods. We enrolled 29 patients without any current evidence of underlying connective tissue disorder and fulfilling the Sapporo preliminary classification criteria for APS. Results. Ten (34,4%) patients showed mild hyperhomocysteinemia (18,34 μmol/L ± 2,04 DS). Nine had history of cerebrovascular disease, isolated (3 cases) or more often (6 cases) in association with other APS features. All patients, but one, showed multiple ischemic cerebral lesions. Seven of the 10 patients with hyperomocysteinemia had multiple antiphospholipid antibody positivity and presented more frequently (6 cases) multidistrectual vascular involvement. Conclusions. The frequency of hyperhomocysteinemia in patients with primary APS is not negligible and appears to be associated with cerebral microangiopathic disease, multiple antiphospholipid antibody positivity and the simultaneous involvement of different vascular districts. For this reason and because hyperhomocysteinemia can be easily corrected with safe and relatively inexpensive therapeutic interventions, we advocate the measurement of homocysteinemia in every patient affected by APS and possibly in subjects with positive antiphospholipid antibody without a history of thrombosis

[Primary antiphospholipid syndrome and hyperhomocysteinemia: a study of a group of 29 patients].

Objective. In order to investigate the potential role of hyperhomocysteinemia as an additional risk factor for thrombotic events, we studied its prevalence in patients with primary antiphospholipid syndrome (APS) and evaluated its association with different clinical features. Methods. We enrolled 29 patients without any current evidence of underlying connective tissue disorder and fulfilling the Sapporo preliminary classification criteria for APS. Results. Ten (34,4%) patients showed mild hyperhomocysteinemia (18,34 μmol/L ± 2,04 DS). Nine had history of cerebrovascular disease, isolated (3 cases) or more often (6 cases) in association with other APS features. All patients, but one, showed multiple ischemic cerebral lesions. Seven of the 10 patients with hyperomocysteinemia had multiple antiphospholipid antibody positivity and presented more frequently (6 cases) multidistrectual vascular involvement. Conclusions. The frequency of hyperhomocysteinemia in patients with primary APS is not negligible and appears to be associated with cerebral microangiopathic disease, multiple antiphospholipid antibody positivity and the simultaneous involvement of different vascular districts. For this reason and because hyperhomocysteinemia can be easily corrected with safe and relatively inexpensive therapeutic interventions, we advocate the measurement of homocysteinemia in every patient affected by APS and possibly in subjects with positive antiphospholipid antibody without a history of thrombosis

Airborne particulate matter (PM) filter analysis and modeling by total reflection X-ray fluorescence (TXRF) and X-ray standing wave (XSW)

This work is presented as an improvement of a recently introduced method for airborne particulate matter (PM) filter analysis [1]. X-ray Standing Wave (XSW) and Total reflection X-Ray Fluorescence (TXRF) were performed with a new dedicated laboratory instrumentation. The main advantage of performing both XSW and TXRF, is the possibility to distinguish the nature of the sample: if it is a small droplet dry residue, a thin film like or a bulk sample; and to select the angle of total reflection to make TXRF measurements. Finally, the possibility to switch the X-ray source allows to measure with more accuracy lighter and heavier elements (with a a change in X-ray anode, for example from Mo to Cu). The aim of the present study is to lay the theoretical foundation of the new proposed method for airborne PM filters quantitative analysis improving the accuracy and efficiency of quantification by means of an external standard. The theoretical model presented and discussed demonstrated that airborne PM filters can be considered as thin layers. A set of reference samples is prepared in laboratory and used to obtain a calibration curve. Our results demonstrate that the proposed method for quantitative analysis of air PM filters is affordable and reliable without the necessity to digest filters to obtain quantitative chemical analysis, and that the use of XRW improve the accuracy of TXRF analysis

Tremor, olfactory and motor changes in Italian adolescents exposed to historical ferro-manganese emission.

Background and objective: Increased prevalence of Parkinsonism was observed in Valcamonica, Italy, a region impacted by ferroalloy plants emissions containing manganese and other metals for a century until 2001. The aim of this study was to assess neurobehavioral functions in adolescents from the impacted region and the reference area of Garda Lake. Methods: Adolescents age 11–14 years were recruited through the school system for neuro-behavioral testing. Metals including manganese, lead, iron, zinc, copper were measured in airborne particulate matter collected with 24-h personal samplers, and in soil, tap water, blood, urine and hair. Independent variables included parental education and socio-economic status, children’s body mass index, number of siblings, parity order, smoking and drinking habits. Results: A total of 311 subjects (49.2% females), residing in either the exposed (n = 154) or the reference (n = 157) area participated. Average airborne and soil manganese were respectively 49.5 ng/m3 (median 31.4, range 1.24–517) and 958 ppm (median 897, range 465–1729) in the impacted area, and 27.4 ng/m3 (median 24.7, range 5.3–85.9) ng/m3 and 427 ppm (median 409 range 160–734) in the reference area. Regression models showed significant impairment of motor coordination (Luria-Nebraska test, p = 0.0005), hand dexterity (Aiming Pursuit test, p = 0.0115) and odor identification (Sniffin’ task, p = 0.003) associated with soil manganese. Tremor intensity was positively associated with blood (p = 0.005) and hair (p = 0.01) manganese. Conclusion: Historical environmental exposure to manganese from ferroalloy emission reflected by the concentration in soil and the biomarkers was associated with sub-clinical deficits in olfactory and motor function among adolescents