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Boronic Acid-Containing 3- pyrazolo[4,3-]quinoline Compounds as Dual CLK/ROCK Inhibitors with Anticancer Properties.
Pharmaceuticals (Basel)
December 2024
Department of Chemistry, Purdue University, 560 Oval Drive, West Lafayette, IN 47907, USA.
The protein kinases CLK and ROCK play key roles in cell growth and migration, respectively, and are potential anticancer targets. ROCK inhibitors have been approved by the FDA for various diseases and CLK inhibitors are currently being trialed in the clinic as anticancer agents. Compounds with polypharmacology are desired, especially in oncology, due to the potential for high efficacy as well as addressing resistance issues.
View Article and Find Full Text PDFKnockout of the Carbohydrate Responsive Element Binding Protein Enhances Proliferation and Tumorigenesis in Renal Tubules of Mice.
Int J Mol Sci
October 2024
Institut für Pathologie, Universitaetsmedizin Greifswald, DE-17489 Greifswald, Germany.
Glycogen-storing so-called clear cell kidney tubules (CCTs), precursor lesions of renal cell carcinoma, have been described in diabetic rats and in humans. The lesions show upregulation of the Akt/mTOR-pathway and the related transcription factor carbohydrate responsive element binding protein (ChREBP), which is supposedly pro-oncogenic. We investigated the effect of ChREBP-knockout on nephrocarcinogenesis in streptozotocin-induced diabetic and normoglycemic mice.
View Article and Find Full Text PDFThe Controversial Role of Glucocorticoids in Atheroembolic Renal Disease: A Narrative Review.
J Clin Med
October 2024
Department of Medicine and Surgery, University of Parma, 43126 Parma, Italy.
Cholesterol crystal embolism (CCE) is an underrecognized multisystemic disease caused by the displacement of cholesterol crystals from atheromatous aortic plaques to distal vascular beds, leading to ischemic injury of target organs, particularly the kidneys, i.e., atheroembolic renal disease (ARD).
View Article and Find Full Text PDF[Convective Methods versus Diffusive Methods: Defined Superiority?].
G Ital Nefrol
October 2024
U.O.C. di Nefrologia , Dialisi ed Ipertensione IRCCS Azienda Ospedaliero-Universitaria di Bologna.
The technique of dialysis has seen enormous advancements over the past fifty years, evolving from an initial phase, primarily based on diffusion through a semipermeable membrane to the current preference for high-efficiency convection, involving the removal of several liters of ultrafiltrate. Diffusive dialysis, due to its relative simplicity in execution, has allowed the treatment of millions of individuals with ESRD, ensuring them a certain quality of life. However, it is not considered optimal in terms of survival and has some complications inherent to the uremic state.
View Article and Find Full Text PDF[Hyperuricemia in Chronic Kidney Disease: To Treat or Not to Treat?].
G Ital Nefrol
October 2024
già Direttore SC Nefrologia e Dialisi, ASO "SS. Antonio e Biagio e C. Arrigo", Alessandria.
Numerous studies have shown that hyperuricemia (HU) is an independent risk factor for the development of chronic kidney disease (CKD) and cardiovascular events. However, while some evidence suggests that uric acid (UA) may play not only a predictive but also a causal role in these conditions, a robust and definitive demonstration of this is still lacking. Moreover, despite what appears to be a logical rationale supporting the use of so-called 'urate-lowering therapy' (ULT) for nephroprotection in hyperuricemic patients with CKD, studies and meta-analyses on this topic - sometimes burdened by limitations that may have affected their results - have so far provided highly divergent outcomes, leaving uncertainty about whether drug-induced reduction of uricemia can truly slow the progression of CKD and prevent its cardiovascular complications.
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