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Impaired insulin signaling is a key feature of type 2 diabetes and is associated with increased ubiquitin-proteasome-dependent protein degradation in skeletal muscle. An extract of Artemisia dracunculus L. (termed PMI5011) improves insulin action by increasing insulin signaling in skeletal muscle. We sought to determine if the effect of PMI5011 on insulin signaling extends to regulation of the ubiquitin-proteasome system. C2C12 myotubes and the KK-Ay murine model of type 2 diabetes were used to evaluate the effect of PMI5011 on steady-state levels of ubiquitylation, proteasome activity and expression of Atrogin-1 and MuRF-1, muscle-specific ubiquitin ligases that are upregulated with impaired insulin signaling. Our results show that PMI5011 inhibits proteasome activity and steady-state ubiquitylation levels in vitro and in vivo. The effect of PMI5011 is mediated by PI3K/Akt signaling and correlates with decreased expression of Atrogin-1 and MuRF-1. Under in vitro conditions of hormonal or fatty acid-induced insulin resistance, PMI5011 improves insulin signaling and reduces Atrogin-1 and MuRF-1 protein levels. In the KK-Ay murine model of type 2 diabetes, skeletal muscle ubiquitylation and proteasome activity is inhibited and Atrogin-1 and MuRF-1 expression is decreased by PMI5011. PMI5011-mediated changes in the ubiquitin-proteasome system in vivo correlate with increased phosphorylation of Akt and FoxO3a and increased myofiber size. The changes in Atrogin-1 and MuRF-1 expression, ubiquitin-proteasome activity and myofiber size modulated by PMI5011 in the presence of insulin resistance indicate the botanical extract PMI5011 may have therapeutic potential in the preservation of muscle mass in type 2 diabetes.

Background/Aims: Endoscopic ultrasound-guided liver biopsy (EUS-LB) is an effective and safe method of procuring liver tissue. The aims of this study were to assess and compare the outcomes and tissue adequacy of a single-pass, single-actuation, wet suction technique between 19 G and 22 G needles in patients undergoing EUS-LB.Methods: We performed a prospective case series study of 20 patients undergoing EUS-LB at a single center between September 2017 and April 2020. The primary objective was to evaluate differences in sample adequacy via a single actuation wet suction technique between a 19 G core needle and a 22 G core needle. Adequacy was gauged by cumulative core biopsy length and the number of portal tracts visualized.Results: The 19 G needle provided a longer core length (2.5 cm vs. 1.2 cm, p<0.0001), more complete portal tracts (5.8 vs. 1.7, p<0.0001), more total tracts (8.8 vs. 3, p<0.0001), and a longer, intact, fragment length (0.75 cm vs. 0.32 cm, p<0.0006). The 19 G needle was superior in providing adequate (60% vs. 5%, p<0.001) and diagnostic pathologic samples (85% vs. 10%, p<0.001).Conclusions: A single-pass, single-actuation, wet suction technique using a 19 G needle is superior to that using a 22 G needle for tissue acquisition and sample adequacy in EUS-LB.

Elevated interleukin-6 (IL-6) levels may correlate with disease severity in COVID-19. We analyzed whether there was an association between elevated IL-6 levels and major adverse cardiac events (MACE) and/or mortality in COVID-19 patients. A retrospective chart review was performed on COVID-19 patients among four hospitals in one health system from March to May 2020, extracting information on baseline characteristics, MACE (i.e., myocardial infarction, stroke, deep venous thrombosis/pulmonary embolism, or shock requiring vasopressor support), mortality, and IL-6 levels. Of the 496 patients hospitalized with COVID-19, 191 patients had an IL-6 level drawn and 68% had elevated IL-6 levels. The elevated IL-6 population had higher odds of developing a MACE compared to the normal IL-6 population ( P < 0.0001, odds ratio [OR] = 5.91, 95% confidence interval [CI] = 2.65–14.11). The elevated IL-6 population also had higher mortality rates (28.2% vs 5%, P = 0.0001, OR = 7.47, 95% CI = 2.19–39.32) and an increased incidence of a MACE and/or mortality (58.78% vs 20.00%, P < 0.0001, OR = 5.7, 95% CI 2.65–12.83) compared to the normal IL-6 population. Elevated IL-6 levels in COVID-19 patients may be associated with MACE and/or mortality. Monitoring IL-6 levels in COVID-19 patients may help risk-stratify patients.