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.

Analysis and Applications of Non-Adaptive and Adaptive Group Testing Methods for COVID-19

Testing strategies for Covid-19 to maximize number of people tested are urgently needed. Recently, it has been demonstrated that RT-PCR has the sensitivity to detect one positive case in a mixed sample of 32 cases [12], In this paper we propose adaptive group testing strategies based on generalized binary splitting (CBS) [5], where we restrict the group test to the largest group that can be used. The method starts by choosing a group from the population to be tested, performing a test on the combined sample from the entire group, and progressively splitting the group further into subgroups. Compared to individual testing at 4% prevalence, we save 74%; at 1% we save 91%; and at .1% we save 98% of tests. We analyze the number of times each sample is used and show that the method is still efficient if we resort to testing a case individually if the sample is running low. In addition we recommend clinical screening to filter out individuals with symptoms and show this leaves us with a population with lower prevalence. Our approach is particularly applicable to vulnerable confined populations such as nursing homes, prisons, military ships and cruise ships.

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.