Weaverjohansen6053

Finally, ETV induces PD-L1 in primary hepatocytes infected by HBV. These results provide evidence that ETV considerably upregulates PD-L1 on the cell surface of infected hepatocytes, which may be one of mechanisms by which infected hepatocytes subvert immune surveillance. © The Japanese Society for Immunology. 2020. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.CONTEXT Vitamin B12 and folate deficiency are not only linked to hematological, neurological and cardiovascular diseases, but also associate with insulin resistance. Metformin can decrease vitamin B12 and folate concentrations. OBJECTIVE To examine (i) effects of short-term metformin treatment on serum holotranscobalamin (holoTC) and folate and (ii) their association with insulin sensitivity in recent-onset type 2 diabetes. DESIGN This cross-sectional analysis comprised patients (known disease duration less then 12 months) on metformin monotherapy (MET, n=123, 81 males, 53±12 years) or non-pharmacological treatment (NPT, n=126, 77 males, 54±11 years) of the German Diabetes Study. MAIN OUTCOME MEASURES HoloTC (ELISA), cobalamin and folate (electrochemiluminescence); beta-cell function and whole-body insulin sensitivity, measured during fasting (HOMA-B, HOMA-IR) and intravenous glucose tolerance tests (IVGTT) combined with hyperinsulinemic-euglycemic clamp tests. RESULTS HoloTC (105.4 [82.4, 128.3] vs. 97 [79.7, 121.9] pmol/L) and folate concentrations (13.4 [9.3, 19.3] vs. 12.7 [9.3, 22.0] nmol/L) were similar in both groups. Overall, holoTC neither associated with fasting nor glucose-stimulated beta-cell function and insulin-stimulated glucose disposal. Cobalamin measurements yielded similar results in representative subgroups. In NPT but not MET, folate levels were inversely correlated with HOMA-IR (r=-0.239, P=0.007). Folate levels neither related to insulin sensitivity nor insulin secretion in the whole cohort and in each group separately after adjustment for age, BMI and sex. CONCLUSIONS Metformin does not affect circulating holoTC and folate concentrations in recent-onset type 2 diabetes, rendering monitoring of vitamin B12 and folate dispensable at least during the first 6 months after diagnosis or initiation of metformin. © Endocrine Society 2020. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.CONTEXT GLP-1 receptor agonists are an established therapy in patients with type 2 diabetes; however, their role in type 1 diabetes remains to be determined. OBJECTIVE Determine efficacy and safety of once-weekly albiglutide 30mg (up-titration to 50mg at week 6) versus placebo together with insulin in patients with new-onset type 1 diabetes and residual insulin production. DESIGN 52-week, randomized, phase 2 study (NCT02284009). METHODS A prespecified Bayesian approach, incorporating placebo data from a prior study, allowed for 31 (albiglutideplacebo) randomization. The primary endpoint was 52-week change from baseline in mixed meal tolerance test (MMTT) stimulated 2-hour plasma C-peptide area under the curve (AUC). Secondary endpoints included metabolic measures and pharmacokinetics of albiglutide. RESULTS 12/17 (70.6%, placebo) and 40/50 (80.0%, albiglutide) patients completed the study. Within our study, mean (SD) change from baseline to week 52 in MMTT-stimulated 2-hour plasma C-peptide AUC was -0.16 nmol/L (0.366) with placebo and -0.13 nmol/L (0.244) with albiglutide. For the primary Bayesian analysis (including prior study data) the posterior treatment difference (95% credible interval) was estimated at 0.12 nmol/L (0-0.24);the probability of a difference ≥0.2 nmol/L between treatments was low (0.097). A transient significant difference in maximum C-peptide was seen at week 28. Otherwise, no significant secondary endpoint differences were noted. . On-therapy adverse events were reported in 82.0% (albiglutide) and 76.5% (placebo) of patients. CONCLUSION In newly diagnosed patients with type 1 diabetes, albiglutide 30‒50 mg weekly for 1 year had no appreciable effect on preserving residual β-cell function versus placebo. © Endocrine Society 2020. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.Synaptic plasticity is the neural basis of physiological processes involved in learning and memory. Tripartite motif-containing 32 (TRIM32) has been found to play many important roles in the brain such as neural stem cell proliferation, neurogenesis, inhibition of nerve proliferation, and apoptosis. TRIM32 has been linked to several nervous system diseases including autism spectrum disorder, depression, anxiety, and Alzheimer's disease. However, the role of TRIM32 in regulating the mechanism of synaptic plasticity is still unknown. Our electrophysiological studies using hippocampal slices revealed that long-term potentiation of CA1 synapses was impaired in TRIM32 deficient (KO) mice. Further research found that dendritic spines density, AMPA receptors, and synaptic plasticity-related proteins were also reduced. NMDA receptors were upregulated whereas GABA receptors were downregulated in TRIM32 deficient mice, explaining the imbalance in excitatory and inhibitory neurotransmission. This caused overexcitation leading to decreased neuronal numbers in the hippocampus and cortex. In summary, this study provides this maiden evidence on the synaptic plasticity changes of TRIM32 deficiency in the brain and proposes that TRIM32 relates the notch signaling pathway and its related mechanisms contribute to this deficit. © The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.Rendered products from the meat industry can provide economical quality sources of proteins to the animal and feed industry. Similar to lipids, rendered proteins are susceptible to oxidation, yet the stability of these proteins is unclear. In addition, interest in understanding how oxidative stress can impact efficiency in production animals is increasing. Recent studies show that consumption of oxidized lipids can lead to a change in oxidative status of the animal, as well as decreases in production efficiency. To date, little is known about how consumption of oxidized proteins impacts oxidative status and growth performance. check details The objectives of this study were to determine if feeding diets high in oxidized protein to growing pigs would 1) impact growth performance, and 2) induce oxidative stress. Thirty pigs (42 d old initial body weight (BW) 12.49 ± 1.45 kg) were randomly assigned to 1 of 3 dietary treatments with increasing levels of oxidized protein. Spray dried bovine plasma was used as the protein source and was either unheated upon arrival, heated at 45°C for 4 d, or heated at 100°C for 3 d.