Diabetic Nephropathy: Novel Molecular Mechanisms and Therapeutic Avenues

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PPARs as new therapeutic targets for the treatment of cerebral ischemia/reperfusion injury.

Stroke is a leading cause of death and long-term disability in industrialized countries. Despite advances in understanding its pathophysiology, little progress has been made in the treatment of stroke. The currently available therapies have proven to be highly unsatisfactory (except thrombolysis) and attempts are being made to identify and characterize signaling proteins which could be exploited to design novel therapeutic modalities. The peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors that control lipid and glucose metabolism. PPARs regulate gene expression by binding with the retinoid X receptor (RXR) as a heterodimeric partner to specific DNA sequences, termed PPAR response elements. In addition, PPARs may modulate gene transcription also by directly interfering with other transcription factor pathways in a DNA-binding independent manner. To date, three different PPAR isoforms, designated α, β/ δ, and γ, have been identified. Recently, they have been found to play an important role for the pathogenesis of various disorders of the central nervous system and accumulating data suggest that PPARs may serve as potential targets for treating ischemic stroke. Activation of all PPAR isoforms, but especially of PPAR γ, was shown to prevent post-ischemic inflammation and neuronal damage in several in vitro and in vivo models, negatively regulating the expression of genes induced by ischemia/ reperfusion (I/R). This paper reviews the evidence and recent developments relating to the potential therapeutic effects of PPAR-agonists in the treatment of cerebral I/R injury

An absorbing boundary formulation for the stratified, linearized, ideal MHD equations based on an unsplit, convolutional perfectly matched layer

Perfectly matched layers are a very efficient and accurate way to absorb waves in media. We present a stable convolutional unsplit perfectly matched formulation designed for the linearized stratified Euler equations. However, the technique as applied to the Magneto-hydrodynamic (MHD) equations requires the use of a sponge, which, despite placing the perfectly matched status in question, is still highly efficient at absorbing outgoing waves. We study solutions of the equations in the backdrop of models of linearized wave propagation in the Sun. We test the numerical stability of the schemes by integrating the equations over a large number of wave periods.Comment: 8 pages, 7 figures, accepted, A &

Intrinsic and Extrinsic Modulators of the Epithelial to Mesenchymal Transition: Driving the Fate of Tumor Microenvironment

The epithelial to mesenchymal transition (EMT) is an evolutionarily conserved process. In cancer, EMT can activate biochemical changes in tumor cells that enable the destruction of the cellular polarity, leading to the acquisition of invasive capabilities. EMT regulation can be triggered by intrinsic and extrinsic signaling, allowing the tumor to adapt to the microenvironment demand in the different stages of tumor progression. In concomitance, tumor cells undergoing EMT actively interact with the surrounding tumor microenvironment (TME) constituted by cell components and extracellular matrix as well as cell secretome elements. As a result, the TME is in turn modulated by the EMT process toward an aggressive behavior. The current review presents the intrinsic and extrinsic modulators of EMT and their relationship with the TME, focusing on the non-cell-derived components, such as secreted metabolites, extracellular matrix, as well as extracellular vesicles. Moreover, we explore how these modulators can be suitable targets for anticancer therapy and personalized medicine

Remarks on hard Lefschetz conjectures on Chow groups

We propose two conjectures of Hard Lefschetz type on Chow groups and prove them for some special cases. For abelian varieties, we shall show they are equivalent to well-known conjectures of Beauville and Murre.Comment: to appear in Sciences in China, Ser. A Mathematic