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Unraveling the therapeutic potential of the Hedgehog pathway in cancer.
We review the preclinical data that continue to shape our understanding of the Hh pathway in tumorigenesis and the emerging clinical experience with smoothened inhibitors....
Mst1 inhibits autophagy by promoting the interaction between Beclin1 and Bcl-2.
We show that Mst1, a proapoptotic kinase, impairs protein quality control mechanisms in the heart through inhibition of autophagy. Stress-induced activation of Mst1 in cardiomyocytes promoted accumulation of p62 and aggresome formation, accompanied by the disappearance of autophagosomes. Mst1 phosph...
Straight talk with...Daniel Levy. Interviewed by Elie Dolgin.
The Framingham Heart Study (FHS) has long been a beacon of biomedical research, yielding landmark findings on everything from the links between elevated blood pressure and stroke to the genetic risk factors underlying cardiac arrhythmias. Now, the fabled 65-year-long study of cardiovascular disease...
Therapeutically reeducating macrophages to treat GBM.
Glioblastoma multiforme (GBM) is the most common type of aggressive malignant brain cancer. The current lack of successful therapeutics means that this disease has a dismal prognosis. However, a new study in mice offers hope for patients with GBM by demonstrating the efficacy of a novel drug that ta...
The hygiene hypothesis.
Endothelial TWIK-related potassium channel-1 (TREK1) regulates immune-cell trafficking into the CNS.
We analyzed the role of TWIK-related potassium channel-1 (TREK1, encoded by KCNK2) in human and mouse endothelial cells and the BBB. TREK1 was downregulated in endothelial cells by treatment with interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α). Blocking TREK1 increased leukocyte transmigrat...
Forever (FGF) 21.
The fibroblast growth factor 21 (FGF21)-β-Klotho pathway orchestrates a switch to oxidative metabolism during fasting and starvation and has been implicated as a signal connecting nutrition, growth, reproduction and longevity. Two new studies in mice show that Fgf21 interacts directly with the brain...
Proliferating macrophages prevail in atherosclerosis.
Macrophages accumulate in atherosclerotic lesions during the inflammation that is part of atherosclerosis development and progression. A new study in mice indicates that the accumulation of macrophages in atherosclerotic plaques depends on local macrophage proliferation rather than the recruitment o...
Inhibition of p300 impairs Foxp3(+) T regulatory cell function and promotes antitumor immunity.
We now report that conditional deletion or pharmacologic inhibition of one HAT, p300 (also known as Ep300 or KAT3B), in Foxp3(+) Treg cells increased T cell receptor-induced apoptosis in Treg cells, impaired Treg cell suppressive function and peripheral Treg cell induction, and limited tumor growth...
Thioredoxin-interacting protein regulates insulin transcription through microRNA-204.
We identified thioredoxin-interacting protein (TXNIP), a cellular redox regulator, as a crucial factor in beta-cell biology and show that beta-cell TXNIP is upregulated in diabetes, whereas TXNIP deficiency protects against diabetes by preventing beta-cell apoptosis. Here we show that TXNIP and diab...