Rothparsons3088

Betaines are food components widely distributed in plants, animals, microorganisms, and dietary sources. Among betaines, δ-valerobetaine (N,N,N-trimethyl-5-aminovaleric acid, δVB) shares a metabolic pathway common to γ-butyrobetaine (γBB). The biological properties of δVB are particularly attractive, as it possesses antioxidant, anti-inflammatory and anticancer activities. Here, we investigated the possible synergism between δVB and the structurally related γBB, to date unexplored, by testing the in vitro anticancer activity in head and neck squamous cell carcinoma cell lines, FaDu, UM-SCC-17A and Cal 27. Among cell lines tested, results indicated that betaines showed the highest effect in reducing Cal 27 cell proliferation up to 72 h (p less then 0.01). This effect was enhanced when betaines were administered in combination (δVB plus γBB) (p less then 0.001). Inhibition of cell growth by δVB plus γBB involved reactive oxygen species (ROS) accumulation, upregulation of sirtuin 1 (SIRT1), and apoptosis (p less then 0.001). SIRT1 gene silencing by small interfering RNA decreased the apoptotic effect of δVB plus γBB by modulating downstream procaspase-3 and cyclin B1 (p less then 0.05). These findings might have important implications for novel prevention strategies for tongue squamous cell carcinoma by targeting SIRT1 with naturally occurring betaines.Preeclampsia (PE) is a pregnancy-specific disorder associated with hypertension and proteinuria. Since there is no proven method to treat PE, early prediction and accurate diagnosis are essential for appropriate management of the disease. Thus, reliable biomarkers for diagnosing PE need to be identified and evaluated. We analyzed serum-soluble factors and miRNAs in 92 patients with PE and an equal number of healthy controls to identify new useful biomarkers for PE. Serum miR-31-5p, miR-155-5p, and miR-214-3p levels were significantly elevated in these patients and highly correlated with clinical symptoms of hypertension and proteinuria, whereas the miR-1290-3p level was decreased. The increased miRNAs were upregulated in an NF-κB-dependent manner and suppressed endothelial nitric oxide synthase (eNOS) and placental growth factor (PlGF) expression. compound 78c mw The level of each miRNA had greater than 90% diagnostic accuracy, which was further increased by analyzing its ratio relative to that of miR-1290-3p. Taken together, the ratios of miR-31-5p, miR-155-5p, or miR-214-3p to miR-1290-3p may serve as reliable diagnostic or prognostic tools for PE, thereby providing evidence that these miRNAs are promising mechanism-based targets for designing therapeutic and preventive strategies for the clinical management of PE.Aortic valve interstitial cells (VICs) constitute a heterogeneous population involved in the maintenance of unique valvular architecture, ensuring proper hemodynamic function but also engaged in valve degeneration. Recently, cells similar to telocytes/interstitial Cajal-like cells described in various organs were found in heart valves. The aim of this study was to examine the density, distribution, and spatial organization of a VIC subset co-expressing CD34 and PDGFRα in normal aortic valves and to investigate if these cells are associated with the occurrence of early signs of valve calcific remodeling. We examined 28 human aortic valves obtained upon autopsy. General valve morphology and the early signs of degeneration were assessed histochemically. The studied VICs were identified by immunofluorescence (CD34, PDGFRα, vimentin), and their number in standardized parts and layers of the valves was evaluated. In order to show the complex three-dimensional structure of CD34+/PDGFRα+ VICs, whole-mount specimens wronment resisting to pathologic remodeling. Their reduced number in older age could limit the self-regenerative properties of the valve stroma.Non-small-cell lung cancer (NSCLC) represents roughly 85% of lung cancers, with an incidence that increases yearly across the world. The introduction in clinical practice of several new and more effective molecules has led to a consistent improvement in survival and quality of life in locally advanced and metastatic NSCLC. In particular, oncogenic drivers have indeed transformed the therapeutic algorithm for NSCLC. Nearly 25% of patients are diagnosed in an early stage when NSCLC is still amenable to radical surgery. In spite of this, five-year survival rates for fully resected early stage remains rather disappointing. Adjuvant chemotherapy has shown a modest survival benefit depending on the stage, but more than half of patients relapse. Given this need for improvement, over the last years different targeted therapies have been evaluated in early-stage NSCLC with no survival benefit in unselected patients. However, the identification of reliable predictive biomarkers to these agents in the metastatic setting, the design of molecularly-oriented studies, and the availability of novel potent and less toxic agents opened the way for a novel era in early stage NSCLC treatment. In this review, we will discuss the current landscape of targeted therapeutic options in early NSCLC.Macrophage is one of the important players in immune response which perform many different functions during tissue injury, repair, and regeneration. Studies using animal models of cardiovascular diseases have provided a clear picture describing the effect of macrophages and their phenotype during injury and regeneration of various vascular beds. Many data have been generated to demonstrate that macrophages secrete many important factors including cytokines and growth factors to regulate angiogenesis and arteriogenesis, acting directly or indirectly on the vascular cells. Different subsets of macrophages may participate at different stages of vascular repair. Recent findings also suggest a direct interaction between macrophages and other cell types during the generation and repair of vasculature. In this short review, we focused our discussion on how macrophages adapt to the surrounding microenvironment and their potential interaction with other cells, in the context of vascular repair supported by evidences mostly from studies using hindlimb ischemia as a model for studying post-ischemic vascular repair.