New sulfurated derivatives of cinnamic acids and rosmaricine as inhibitors of STAT3 and NF-kappa B transcription factors

A set of new sulfurated drug hybrids, mainly derived from caffeic and ferulic acids and rosmaricine, has been synthesized and their ability to inhibit both STAT3 and NF-kappa B transcription factors have been evaluated. Results showed that most of the new hybrid compounds were able to strongly and selectively bind to STAT3, whereas the parent drugs were devoid of this ability at the tested concentrations. Some of them were also able to inhibit the NF-kappa B transcriptional activity in HCT-116 cell line and inhibited HCT-116 cell proliferation in vitro with IC50 in micromolar range, thus suggesting a potential anticancer activity. Taken together, our study described the identification of new derivatives with dual STAT3/NF-kappa B inhibitory activity, which may represent hit compounds for developing multi-target anticancer agents

Simultaneous evaluation of multiple microarray surface chemistries through real-time interferometric imaging.

Surface chemistry is a crucial aspect for microarray modality biosensor development. The immobilization capability of the functionalized surface is indeed a limiting factor for the final yield of the binding reaction. In this work, we were able to simultaneously compare the functionality of protein ligands that were locally immobilized on different polymers, while on the same solid support, therefore demonstrating a new way of multiplexing. Our goal was to investigate, in a single experiment, both the immobilization efficiency of a group of reactive polymers and the resulting affinity of the tethered molecules. This idea was demonstrated by spotting many reactive polymers on a Si/SiO2 chip and depositing the molecular probes on the spots immediately after. As a proof of concept, we focused on which polymers would better immobilize a model protein (α-Lactalbumin) and a peptide (LAC-1). We successfully showed that this protocol is applicable to proteins and peptides with a good efficiency. By means of real-time binding measurements performed with the interferometric reflectance imaging sensor (IRIS), local functionalization proved to be comparable to the classical flat coating solution. The final outcome highlights the multiplexing power of this method: first, it allows to characterize dozens of polymers at once. Secondly, it removes the limitation, related to coated surfaces, that only molecules with the same functional groups can be tethered to the same solid support. By applying this protocol, many types of molecules can be studied simultaneously and immobilization for each probe can be individually optimized.766466 (INDEX) - Horizon 2020 Framework Programmehttps://s3-eu-west-1.amazonaws.com/itempdf74155353254prod/8976347/Simultaneous_Evaluation_of_Multiple_Microarray_Surface_Chemistries_Through_Real-Time_Interferometric_Imaging_v1.pdfFirst author draf

RF-Assisted Free-Space Optics for 5G Vehicle-to-Vehicle Communications

Vehicle-to-Vehicle (V2V) communications are being proposed, tested and deployed to improve road safety and traffic efficiency. However, the automotive industry poses strict requirements for safety-critical applications, that call for reliable, low latency and high data rate communications. In this context, it is widely agreed that both Radio-Frequency (RF) technologies at mmWaves and Free-Space Optics (FSO) represent promising solutions, although their performances are severely degraded by transmitter-receiver misalignment due to the challenging high-mobility conditions. By combining RF and FSO technologies, this paper proposes a FSO-based V2V communication system where the pointing coordinates of laser sources are based on vehicle's information exchanged over a reliable low-rate RF link. Numerical simulations demonstrate that such compensation mechanism is mandatory to counteract the unavoidable misalignments induced by vehicle dynamics, and thus to enable FSO technology for V2V communications even in high mobility scenarios.Comment: Accepted in IEEE ICC 201

Seasonality and Sleep: A Clinical Study on Euthymic Mood Disorder Patients

Background. Research on mood disorders has progressively focused on the study of seasons and on the mood in association with them during depressive or manic episodes yet few studies have focused on the seasonal fluctuation that characterizes the patient's clinical course both during an illness episode and during euthymic periods. Methods. 113 euthymic outpatients 46 affected by major recurrent depression and 67 affected by bipolar disorder were recruited. We evaluated the impact of clinical “rhythmical” factors: seasonality, sleep disturbance, and chronotype. Patients completed the SPAQ+ questionnaire, the MEQ questionnaire, and the medical outcomes study (MOS) sleep scale. We used t-test analyses to compare differences of clinical “rhythmical” and sociodemographic variables and of differences in the assessment scales among the diagnostic groups. Results. Patients reporting a family history for mood disorders have higher fluctuations throughout seasons. Sleep disturbance is more problematic in unipolars when compared to bipolars. Conclusions. Sleep, light, and seasonality seem to be three interconnected features that lie at the basis of chronobiology that, when altered, have an important effect both on the psychopathology and on the treatment of mood disorders

A novel approach for the purification and proteomic analysis of pathogenic immunglobulin free light chains from serum

An excess of circulating monoclonal free immunoglobulin light chains (FLC) is common in plasma cell disorders. A subset of FLC, as amyloidogenic ones, possess intrinsic pathogenicity. Because of their complex purification, little is known on the biochemical features of serum FLC, possibly related to their pathogenic spectrum. We developed an immunopurification approach to isolate serum FLC from patients with monoclonal gammopathies, followed by proteomic characterization. Serum monoclonal FLC were detected and quantified by immunofixation and immunonephelometry. Immunoprecipitation was performed by serum incubation with agarose beads covalently linked to polyclonal anti-κ or λ FLC antibodies. Isolated FLC were analyzed by SDS-PAGE, 2D-PAGE, immunoblotting, mass spectrometry (MS). Serum FLC were immunoprecipitated from 15 patients with ALλ amyloidosis (serum λ FLC range: 98-2350mg/L), 5 with ALκ amyloidosis and 1 with κ light chain (LC) myeloma (κ FLC range: 266-2660mg/L), and 3 controls. Monoclonal FLC were the prevalent eluted species in patients. On 2D-PAGE, both λ and κ FLC originated discrete spots with multiple pI isoforms. The nature of eluted FLC and coincidence with the LC sequence from the bone marrow clone was confirmed by MS, which also detected post-translational modifications, including truncation, tryptophan oxidation, cysteinylation, peptide dimerization. Serum FLC were purified in soluble form and adequate amounts for proteomics, which allowed studying primary sequence and detecting post-translational modifications. This method is a novel instrument for studying the molecular bases of FLC pathogenicity, allowing for the first time the punctual biochemical description of the circulating forms

REGIONAL MAPPING OF MYOCARDIAL HIBERNATION PHENOTYPE IN IDIOPATHIC END-STAGE DILATED CARDIOMYOPATHY

Myocardial hibernation (MH) is a well-known feature of human ischaemic cardiomyopathy (ICM), whereas its presence in human idiopathic dilated cardiomyopathy (DCM) is still controversial. We investigated the histological and molecular features of MH in left ventricle (LV) regions of failing DCM or ICM hearts. We examined failing hearts from DCM (n = 11; 41.9 ± 5.45 years; left ventricle-ejection fraction (LV-EF), 18 ± 3.16%) and ICM patients (n = 12; 58.08 ± 1.7 years; LVEF, 21.5 ± 6.08%) undergoing cardiac transplantation, and normal donor hearts (N, n = 8). LV inter-ventricular septum (IVS) and antero-lateral free wall (FW) were transmurally (i.e. sub-epicardial, mesocardial and sub-endocardial layers) analysed. LV glycogen content was shown to be increased in both DCM and ICM as compared with N hearts (P < 0.001), with a U-shaped transmural distribution (lower values in mesocardium). Capillary density was homogenously reduced in both DCM and ICM as compared with N (P < 0.05 versus N), with a lower decrease independent of the extent of fibrosis in sub-endocardial and sub-epicardial layers of DCM as compared with ICM. HIF1-α and nestin, recognized ischaemic molecular hallmarks, were similarly expressed in DCM-LV and ICM-LV myocardium. The proteomic profile was overlapping by ~50% in DCM and ICM groups. Morphological and molecular features of MH were detected in end-stage ICM as well as in end-stage DCM LV, despite epicardial coronary artery patency and lower fibrosis in DCM hearts. Unravelling the presence of MH in the absence of coronary stenosis may be helpful to design a novel approach in the clinical management of DCM

The Protein Network in Subcutaneous Fat Biopsies from Patients with AL Amyloidosis: More Than Diagnosis?

AL amyloidosis is caused by the misfolding of immunoglobulin light chains leading to an impaired function of tissues and organs in which they accumulate. Due to the paucity of -omics profiles from undissected samples, few studies have addressed amyloid-related damage system wide. To fill this gap, we evaluated proteome changes in the abdominal subcutaneous adipose tissue of patients affected by the AL isotypes κ and λ. Through our retrospective analysis based on graph theory, we have herein deduced new insights representing a step forward from the pioneering proteomic investigations previously published by our group. ECM/cytoskeleton, oxidative stress and proteostasis were confirmed as leading processes. In this scenario, some proteins, including glutathione peroxidase 1 (GPX1), tubulins and the TRiC complex, were classified as biologically and topologically relevant. These and other results overlap with those already reported for other amyloidoses, supporting the hypothesis that amyloidogenic proteins could induce similar mechanisms independently of the main fibril precursor and of the target tissues/organs. Of course, further studies based on larger patient cohorts and different tissues/organs will be essential, which would be a key point that would allow for a more robust selection of the main molecular players and a more accurate correlation with clinical aspects

White muscle disease in three selenium deficient beef and dairy calves in Argentina and Uruguay

White muscle disease (WMD), nutritional myodegeneration or enzootic muscular dystrophy, is a nutritional condition associated with selenium and/or vitamin E deficiency in ruminants. These elements are constituents of the major body antioxidant systems. Depletion of selenium results in oxidative damage to cardiac and skeletal muscle cells, resulting in myodegeneration and myonecrosis, typical lesions of WMD. Selenium deficiency is common in South America, but WMD is underreported. This research describes clinical, biochemical and pathological findings in two episodes of WMD associated with selenium deficiency in beef and dairy calves in Argentina and Uruguay with concurrent copper deficiency in one of them, which resulted in spontaneous calf mortality. Further studies are necessary to estimate the true incidence and economic impact of clinical and subclinical mineral deficiencies in livestock production systems in the southern cone of South America.Doença do músculo branco (DMB), miodegeneração nutricional ou distrofia muscular enzoótica é uma condição nutricional associada à deficiência de selênio e/ou vitamina E em ruminantes. Esses elementos são constituintes dos principais sistemas antioxidantes do corpo. O esgotamento de selênio resulta em dano oxidativo às células musculares cardíacas e esqueléticas, resultando em miodegeneração e mionecrose, lesões típicas da DMB. A deficiência de selênio é comum na América do Sul, mas a DMB está subnotificada. Este trabalho descreve os achados clínicos, bioquímicos e patológicos em dois surtos de DMB associados à deficiência de selênio em bezerros para carne e leite na Argentina e Uruguai com concomitante deficiência de cobre em um surto, que resultaram em mortalidade espontânea de bezerros. São necessários mais estudos para estimar a verdadeira incidência e impacto econômico das deficiências minerais clínicas e subclínicas nos sistemas de produção pecuária no sul da América do Sul.EEA Cuenca del SaladoFil: Rodriguez, Alejandro Martin. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Cuenca del Salado; ArgentinaFil: Schild, Carlos Omar. Instituto Nacional de Investigación Agropecuaria (INIA), La Estanzuela; UruguayFil: Canton, German Jose. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Balcarce; ArgentinaFil: Riet‐Correa, Franklin. Instituto Nacional de Investigación Agropecuaria (INIA), La Estanzuela; UruguayFil: Armendano, Joaquín Ignacio. Universidad Nacional de Mar del Plata. Facultad de Ciencias Agrarias; ArgentinaFil: Caffarena, Rubén Dario. Instituto Nacional de Investigación Agropecuaria (INIA), La Estanzuela; UruguayFil: Brambilla, Emilio Cesar. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Balcarce; ArgentinaFil: García, Juan Agustín. Universidad de la República. Centro Universitario Regional Este; UruguayFil: Morrell, Eleonora Lidia. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Balcarce; ArgentinaFil: Poppenga, Robert. University of California at Davis. School of Veterinary Medicine. California Animal Health and Food Safety (CAHFS). Laboratory; Estados UnidosFil: Giannitti, Federico. Instituto Nacional de Investigación Agropecuaria (INIA), La Estanzuela; Uruguay. University of Minnesota. College of Veterinary Medicine. Veterinary Population Medicine Department; Estados Unido