Novel substituted tetrathia[7]helicenes by direct functionalization of the helical system or photocyclization of substituted 1,2-(bis-benzodithienyl)ethenes

In this work we report the synthesis of several new tetrathia[7]helicenes ([7]THs) functionalized with different electron-donor (ED) and electron-acceptor (EA) substituents in the positions 2,13 (the \u3b1 positions of terminal thiophene rings) and/or 7,8 (on the central arene ring of the helical system). Some substituents were chosen on the basis of theoretical calculations performed on [7]THs to predict the best groups for applications in optoelectronics; some others were conceived to endow helicenes with appropriate groups in view of their insertion into polymeric structures

Sintesi e caratterizzazione di nuovi sistemi tetratia[7]elicenici, molecole con interessanti proprietà ottiche non lineari

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Synthesis and functionalization of novel tetrathia[7]helicenes as new push-pull systems

The synthesis of functionalized 1,2-bis(benzodithienyl)ethenes and the prepn. of the corresponding tetrathia[7]helicenes are described. The helicenes reported are chiral push-pull mols., with potential application in optoelectronics. Functionalized tetrathia[7]helicenes are obtained in good yields by application of two different synthetic strategies: (1) introduction of functionalized groups onto the alkene precursor followed by photochem. cyclization or (2) direct functionalization of the helicene

Sirolimus vs cyclosporine after induction with basiliximab does not promote regulatory T cell expansion in de novo kidney transplantation: Results from a single-center randomized trial

none12noRegulatory T cells (Tregs), defined as CD4+CD25+highFoxP3+CD127- cells, could promote tolerance in renal transplantation (Tx). In an open-label, randomized, controlled trial 62 de-novo Tx recipients received induction with basiliximab and cyclosporine A (CsA) for the first month after Tx and then were assigned to treatment with sirolimus (SRL) or CsA and followed up for 2years. The primary endpoint was to evaluate the effects of induction and maintenance treatments on circulating Tregs, while the secondary endpoint was the assessment of Treg renal infiltration and the relationship between Treg count and clinical outcomes. There were no significant differences in either circulating or tissue Treg number between the two groups. At 1month post-Tx, all patients presented a profound Treg depletion, followed by a significant increase in Tregs that resulted stable during the follow-up. The same trend was also observed for non-activated Tregs (CD69-) and for other immunocompetent cells (CD4+ and CD8+ T cells, B cells and NK cells). Moreover, the Treg count did not correlate either with renal function or with acute rejection and graft loss. Initial immunosuppression is crucial to regulate circulating Tregs, regardless of subsequent immunosuppressive maintenance regimens. Strategies aiming to promote tolerance should consider the effects of different induction regimens.openLibetta, Carmelo; Esposito, Pasquale; Gregorini, Marilena; Margiotta, Elisa; Martinelli, Claudia; Borettaz, Ilaria; Canevari, Michele; Rampino, Teresa; Ticozzelli, Elena; Abelli, Massimo; Meloni, Federica; Dal Canton, AntonioLibetta, Carmelo; Esposito, Pasquale; Gregorini, Marilena; Margiotta, Elisa; Martinelli, Claudia; Borettaz, Ilaria; Canevari, Michele; Rampino, Teresa; Ticozzelli, Elena; Abelli, Massimo; Meloni, Federica; DAL CANTON, Antoni

Myostatin in the arterial wall of patients with end-stage renal disease

Aim: Myostatin (Mstn) has been described as a trigger for the progression of atherosclerosis. In this study, we evaluated the role of Mstn in arterial remodeling in patients with end-stage renal disease (ESRD). Methods: Vascular specimens were collected from 16 ESRD patients (56.4±7.9 years) undergoing renal transplant (recipients) and 15 deceased kidney non-uremic donors (55.4±12.1 years). We studied gene and protein expression of Mstn, ubiquitin ligases, Atrogin-1, and muscle ring finger protein-1 (MuRF-1), inflammatory marker CCL2, cytoskeleton components, and Klotho by reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry. Moreover, we assessed vascular calcification and collagen deposition. Finally, we studied the effects of recombinant Mstn on rat vascular smooth muscle cells (VSMCs, A7r5) and evaluated the effects of uremic serum (US) on primary human VSMCs. Results: Myostatin mRNA was upregulated in the arterial vascular wall of recipients compared with donors (~15-folds, p＜0.05). This response was accompanied by the upregulation of gene expression of Atrogin-1 and MuRF-1 (＋2.5-and ＋10-fold) and CCL2 (＋3-fold). Conversely, we found downregulation of protein expression of Smoothelin, α-smooth muscle actin (α-SMA), vimentin, and Klotho (-85%,-50%,-70%, and-80%, respectively; p＜0.05) and gene expression of vimentin and Klotho. Exposition of A7r5 to Mstn induced a time-dependent SMAD 2/SMAD 3 phosphorylation and expression of collagen-1 and transforming growth factor β (TGFβ) mRNA, while US induced overexpression of Mstn and Atrogin-1 and downregulation of Smoothelin and Klotho. Conclusions: Our data suggest that uremia might induce vascular Mstn gene expression together with a complex pathway of molecular and structural changes in the vascular wall. Myostatin, in turn, can translate the metabolic alterations of uremia into profibrotic and stiffness inducing signals

Understanding Bone Damage After Kidney Transplantation: A\ua0Retrospective Monocentric Cross Sectional Analysis

Background. Kidney transplantation (KT) immunosuppression may induce bone tissue damage with bone mineral density (BMD) loss increasing bone fractures risk. Steroid therapy is considered the major player, but others factors are still under review.Patients and Methods. We designed an observational retrospective cohort study to evaluate bone damage after KT. The prevalence of osteopenia, osteoporosis, bone fractures, and the associated risk factors were investigated. The following parameters were recorded before transplantation and at the last follow-up: demographic indexes, cumulative steroid dose (CSD), dialytic and transplantologic age, previous nephropathy, femoral and lumbar BMD, fractures, immunosuppressors, calcemia, phosphoremia, rejection episodes, estimated glomerular filtration rate, and parathyroid hormone and vitamin D levels. Stata software (Stata Corporation, College Station, Texas, United States) was used for the statistical analysis, to perform the Fisher's exact test, Kruskal-Wallis test, Student t test, as well as univariate and multivariate analyses.Results. The analyzed cohort was composed of 297 patients (65.3% males and 34.7% females). Sixty percent of KT patients had normal BMD, 24% had osteopenia, and 15% had osteoporosis. Twelve percent were victims of bone fractures (8.4% minor, 2% femoral, and 1.7% vertebral). A significant correlation (P <.05) was observed for both osteopenia and osteoporosis with menopause, transplantologic age, CSD, previous glomerulonephritis, and mammalian target of rapamycin (mTOR) inhibitors treatment (imTOR).Conclusion. This study confirms the correlation between CSD (both before and after transplantation) and post -transplantation bone damage. It also shows that a large fraction of these patients had normal BMD related with a low steroid dose in our protocols. This correlation between imTOR assumption and osteoporosis deserves attention and warrants further in vitro analyses to be performed