RNA-binding protein HuR reprograms immune T cells and promotes oral squamous cell carcinoma.

Hu Antigen R, also known as ELAVL1 (HuR), is a key posttranscriptional regulator in eukaryotic cells. HuR overexpression promotes several malignancies, including head and neck squamous cell carcinoma (HNSCC). However, its immune dysfunction-associated tumorigenesis pathways remain unknown. We examined HuR's effects on oral malignancies and immune cell function in vitro and in vivo using oral carcinoma cells and transgenic HuR knockout (KO) mice. CRISPR/Cas9-mediated HuR deletion in mice syngeneic oral cancer cells eliminated colony formation and tumor development. HuR-KO tumors had a lower tumor volume, fewer CD4+CD25+FoxP3+ regulatory T cells, and more CD8+ T cells, suggesting that HuR may suppress the immune response during oral cancer progression. In contrast, HuR KO oral epithelial tissues are resistant to 4NQO-induced oral malignancies compared to control tumor-bearing mice. HuR KO mice showed fewer Tregs and greater IFN levels than WT tumor-bearing mice, suggesting anticancer activity. Finally, the HuR inhibitor pyrvinium pamoate lowers tumor burden by enhancing CD8+ infiltration at the expense of CD4+, suggesting anticancer benefits. Thus, HuR-dependent oral neoplasia relies on immunological dysfunction, suggesting that decreasing HuR may boost antitumor potential and offer a novel HNSCC therapy.

Levo-propionyl-carnitine improves the effectiveness of supervised physical training on the absolute claudication distance in patients with intermittent claudication.

The mechanisms by which supervised physical training improves walking ability in patients with intermittent claudication (IC) are microcirculatory, rheological, and metabolic. The main mechanism of levo-propionylcarnitine (LPC) is metabolic; it increases the walking ability in claudicants, providing an additional energy to the ischemic muscle by an anaplerotic activity. Therefore, the current study was carried out to ascertain whether the combined treatment has a synergistic effect. The results confirm the effectiveness of supervised physical training in patients with IC, and we recommend the use of LPC during the exercise training program, at least in patients with severe claudication. Finally, underlining the similar mechanisms of physical training and LPC treatment, the study suggests that a cycle of LPC infusions could be advised in patients with severe claudication who cannot be included, for various reasons, in an exercise rehabilitation program.