Publications by authors named "A J Provenzani"

HSPB1 [heat shock protein family B (small) member 1] and HSPB8 are essential molecular chaperones for neuronal proteostasis, as they prevent protein aggregation. Mutant HSPB1 and HSPB8 primarily harm peripheral neurons, resulting in axonal Charcot-Marie-Tooth neuropathies (CMT2). Macroautophagy/autophagy is a shared mechanism by which HSPB1 and HSPB8 mutations cause neuronal dysfunction.

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Human antigen R (HuR) is an RNA binding protein (RBP) belonging to the ELAV (Embryonic Lethal Abnormal Vision) family, which stabilizes mRNAs and regulates the expression of multiple genes. Its altered expression or localization is related to pathological features such as cancer or inflammation. Dihydrotanshinone I (DHTS I) is a naturally occurring, tetracyclic ortho-quinone inhibitor of the HuR-mRNA interaction.

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Background And Aims: The aim of this systematic review was to assess the risk of cardiac toxicity in patients undergoing approved PD-1 (nivolumab, pembrolizumab, cemiplimab, dostarlimab), PD-L1 (atezolizumab, avelumab, durvalumab), and CTLA-4 (ipilimumab) inhibitors.

Results: Among a total of 2272 articles, 11 phase II and III clinical trials included: 5463 patients and 175 cardiac adverse events. The most common cardiac disorder was atrial fibrillation (12 %), while cardiac arrest and cardiac failure (6 %) led to death in three cases.

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Article Synopsis
  • The RNA binding protein HuR is crucial for regulating the innate immune response, and blocking it can have positive anti-inflammatory outcomes.
  • A new series of small molecules, Tanshinone Mimics (TMs), were developed to disrupt HuR-RNA binding, with furan-containing compound 5/TM11 proving to be the most effective in inhibiting this interaction.
  • Compound 5/TM11 not only enhances solubility but also selectively decreases cell proliferation in macrophages at certain doses, leading to a significant reduction in proinflammatory cytokines in response to LPS.
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