Hovekrarup0295

RESULTS The cavernous expression of DKK3 protein was significantly lower in the diabetic mice than in controls. DKK3 peptide or adenovirus significantly improved erectile function in diabetic mice (70% of the control values). DKK3 adenovirus profoundly restored cavernous endothelial cell and pericyte contents and increased endothelial junction proteins in diabetic mice in vivo. DKK3 peptide induced up-regulation of angiogenic factors (angiopoietin-1, vascular endothelial growth factor, and basic fibroblast growth factor) and accelerated tube formation in MCECs cultivated under the high-glucose condition in vitro. CONCLUSION DKK3 restored cavernous vascular integrity and improved erectile function in diabetic mice. Therapeutic cavernous angiogenesis by use of DKK3 will be a promising therapeutic strategy to treat diabetic erectile dysfunction. This article is protected by copyright. All rights reserved.OBJECTIVE This study aimed to test the hypothesis that young adults with obesity and cold-activated brown adipose tissue (BAT) are less likely to have metabolic dysfunction (dyslipidemia, insulin resistance, and hypertension) than those without cold-activated BAT. Previous studies have noted a potentially protective effect of BAT and higher adiponectin/leptin ratios, but they have acknowledged that the clinical implications of these findings remain uncertain. METHODS Twenty-one females and twenty-three males with obesity (BMI ≥ 30 kg/m2 ) underwent a 2-hour cooling protocol before 18 F-fluorodeoxyglucose (18 F-FDG)-positron emission tomography/x-ray computed tomography scan to determine the prevalence, volume, and 18 F-FDG uptake of cold-activated BAT. RESULTS Cold-activated BAT was identified in 43% of participants (11 female, 8 male); females had greater 18 F-FDG uptake. Those with cold-activated BAT had a lesser degree of metabolic dysfunction. Cold-activated BAT volume correlated with triglycerides (inversely) and adiponectin (concordantly). Body-mass-adjusted cold-activated BAT activity correlated with high-density lipoprotein cholesterol (concordantly). Males with cold-activated BAT had lower leptin and higher adiponectin/leptin ratio. CONCLUSIONS A high prevalence of cold-activated BAT was found in the study participants. BAT could be important in decreasing metabolic dysfunction among young adults with obesity, making it a potential target for treating metabolically unhealthy obesity. © 2020 The Obesity Society.OBJECTIVE Progressive rheumatoid arthritis (RA) is responsible for joint damage causing disabilities, but there is no agreement on which disease measures best predict radiographic progression. We aimed to determine which disease activity measures, including the disease activity score, the modified disease activity score in 28 joints with C-reactive protein testing (M-DAS28-CRP), the Clinical Disease Activity Index, and the Health Assessment Questionnaire Disability Index, at baseline and 3 months best predicted rapid radiographic progression (RRP) in patients with early RA. METHODS Data were used from PREMIER, a 2-year, multicenter, double-blind, active comparator controlled study with methotrexate (MTX)-naïve patients with RA and active disease for less than 3 years. Treatments included adalimumab plus oral MTX, adalimumab, or oral MTX. Only patients in the MTX arm were analyzed in this study. RRP was defined as a change in the modified total Sharp score of less than 3.5 at month 12. The logistic regression improves prediction of RRP. © 2020 The Authors. ACR Open Rheumatology published by Wiley Periodicals, Inc. on behalf of American College of Rheumatology.Transglutaminases (TGs) play important roles in the food industry, pharmacology and biotechnology, but as protein cross-linkers, their complexes are stable, resistant, immunogenic and potentially pathogenic. Aurora Kinase inhibitor Many TGs have been characterized, but they operate in narrow temperature and pH range limits. In a research article in this issue, Clemens Furnes and colleagues describe a novel cold-adapted transglutaminase from Atlantic cod, which expands the operating boundaries to a lower temperature and a wider pH. In this accompanying commentary, we discuss how this TG opens new applications in cold environments and can be deactivated by heating. New sources of transglutaminases should be explored in hot environments like hot springs, in order to increase the temperature and widen the pH ranges for human and industrial benefits. This article is protected by copyright. All rights reserved.PURPOSE Exertional heat stress adversely distrupts (GI) barrier integrity and, through subsequent microbial translocation (MT), negativly impacts health. Despite widespread application, the temporal reliability of popular GI barrier integity and MT biomarkers is poorly characterised. METHOD Fourteen males completed two 80-min exertional heat stress tests (EHST) separated by 7-14 days. Venous blood was drawn pre, immediately- and 1-hr post both EHSTs. GI barrier integrity was assessed using the serum Dual-Sugar Absorption Test (DSAT), Intestinal Fatty-Acid-Binding Protein (I-FABP) and Claudin-3 (CLDN-3). MT was assessed using plasma Lipopolysaccharide Binding Protein (LBP), total 16S bacterial DNA and Bacteroides DNA. RESULTS No GI barrier integrity or MT biomarker, except absolute Bacteroides DNA, displayed systematic trial order bias (p ≥ .05). I-FABP (trial 1 = Δ 0.834 ± 0.445 ng ml-1 ; trial 2 = Δ 0.776 ± 0.489 ng ml-1 ) and CLDN-3 (trial 1 = Δ 0.317 ± 0.586 ng ml-1 ; trial 2 = Δ 0.371 ± 0.508 ng ml-1 ) were increased post-EHST (p ≤ .01). All MT biomarkers were unchanged post-EHST. Coefficient of variation and typical error of measurement post-EHST were 11.5% and 0.004 (ratio) for the DSAT 90-min postprobe ingestion; 12.2% and 0.004 (ratio) at 150-min postprobe ingestion; 12.1% and 0.376 ng ml-1 for I-FABP; 4.9% and 0.342 ng ml-1 for CLDN-3; 9.2% and 0.420 µg ml-1 for LBP; 9.5% and 0.15 pg µl-1 for total 16S DNA; and 54.7% and 0.032 for Bacteroides/total 16S DNA ratio. CONCLUSION Each GI barrier integrity and MT translocation biomarker, except Bacteroides/total 16S ratio, had acceptable reliability at rest and postexertional heat stress. © 2020 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.