Cofilin Activation in Peripheral CD4 T Cells of HIV-1 Infected Patients: A Pilot Study

Cofilin is an actin-depolymerizing factor that regulates actin dynamics critical for T cell migration and T cell activation. In unstimulated resting CD4 T cells, cofilin exists largely as a phosphorylated inactive form. Previously, we demonstrated that during HIV-1 infection of resting CD4 T cells, the viral envelope-CXCR4 signaling activates cofilin to overcome the static cortical actin restriction. In this pilot study, we have extended this in vitro observation and examined cofilin phosphorylation in resting CD4 T cells purified from the peripheral blood of HIV-1-infected patients. Here, we report that the resting T cells from infected patients carry significantly higher levels of active cofilin, suggesting that these resting cells have been primed in vivo in cofilin activity to facilitate HIV-1 infection. HIV-1-mediated aberrant activation of cofilin may also lead to abnormalities in T cell migration and activation that could contribute to viral pathogenesis.Department of Defense (National Defense Science and Engineering Fellowship); National Institute of Allergy and Infectious Diseases (AI069981

The role of taxes and their importance in China's budget revenues

The article examines the role of taxes, the composition and structure of taxes in China's budget revenues, trends in tax revenues

PEGylated exenatide injection (PB-119) improves beta-cell function and insulin resistance in treatment-naïve type 2 diabetes mellitus patients

Objective: PB-119, a PEGylated exenatide injection, is a once-weekly glucagon-like peptide-1 receptor agonist. In the present study, we aimed to evaluate the effects of PB-119 on insulin resistance and beta-cell function in Chinese patients with type 2 diabetes mellitus (T2DM) to uncover its antidiabetic characteristics.Methods: A total of 36 Chinese T2DM patients were randomized to receive 25 μg and 50 μg PB-119 once weekly and exenatide (5–10 μg injected under the skin 2 times a day adjusted by the doctor) for 12 weeks. Oral mixed meal tolerance tests were conducted before the study and on Day 79. The data were fitted to estimate beta-cell function and insulin sensitivity parameters using the SAAM II package integrating the oral minimal model (OMM), which was compared with Homeostatic Model Assessment (HOMA) analysis results.Results: Exenatide or PB-119 treatment, compared with their baseline, was associated with higher beta-cell function parameters (φb, φs and φtot), disposition index, insulin secretion rates, and a lower glucose area under the curve. High-dose PB-119 also has a higher insulin resistance parameter (SI) than the baseline, but HOMA-IR did not. For the homeostatic model assessment parameters, HOMA-IR showed no statistically significant changes within or between treatments. Only high-dose PB-119 improved HOMA-β after 12 weeks of treatment.Conclusion: After 12 weeks of treatment, PB-119 decreased glycemic levels by improving beta-cell function and insulin resistance