PPARβ/δ Regulates Glucocorticoid- and Sepsis-Induced FOXO1 Activation and Muscle Wasting

FOXO1 is involved in glucocorticoid- and sepsis-induced muscle wasting, in part reflecting regulation of atrogin-1 and MuRF1. Mechanisms influencing FOXO1 expression in muscle wasting are poorly understood. We hypothesized that the transcription factor peroxisome proliferator-activated receptor β/δ (PPARβ/δ) upregulates muscle FOXO1 expression and activity with a downstream upregulation of atrogin-1 and MuRF1 expression during sepsis and glucocorticoid treatment and that inhibition of PPARβ/δ activity can prevent muscle wasting. We found that activation of PPARβ/δ in cultured myotubes increased FOXO1 activity, atrogin-1 and MuRF1 expression, protein degradation and myotube atrophy. Treatment of myotubes with dexamethasone increased PPARβ/δ expression and activity. Dexamethasone-induced FOXO1 activation and atrogin-1 and MuRF1 expression, protein degradation, and myotube atrophy were inhibited by PPARβ/δ blocker or siRNA. Importantly, muscle wasting induced in rats by dexamethasone or sepsis was prevented by treatment with a PPARβ/δ inhibitor. The present results suggest that PPARβ/δ regulates FOXO1 activation in glucocorticoid- and sepsis-induced muscle wasting and that treatment with a PPARβ/δ inhibitor may ameliorate loss of muscle mass in these conditions

Gabriel Triangulations and Angle-Monotone Graphs: Local Routing and Recognition

A geometric graph is angle-monotone if every pair of vertices has a path between them that---after some rotation---is $x$- and $y$-monotone. Angle-monotone graphs are $\sqrt 2$-spanners and they are increasing-chord graphs. Dehkordi, Frati, and Gudmundsson introduced angle-monotone graphs in 2014 and proved that Gabriel triangulations are angle-monotone graphs. We give a polynomial time algorithm to recognize angle-monotone geometric graphs. We prove that every point set has a plane geometric graph that is generalized angle-monotone---specifically, we prove that the half-$\theta_6$-graph is generalized angle-monotone. We give a local routing algorithm for Gabriel triangulations that finds a path from any vertex $s$ to any vertex $t$ whose length is within $1 + \sqrt 2$ times the Euclidean distance from $s$ to $t$. Finally, we prove some lower bounds and limits on local routing algorithms on Gabriel triangulations.Comment: Appears in the Proceedings of the 24th International Symposium on Graph Drawing and Network Visualization (GD 2016

Oxidative stress and its association with ST resolution and clinical outcome measures in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention

Objective: Reperfusion of ischemic myocardium generates oxidative stress, which itself can mediate myocardial injury. So, in this study, we investigated the level of oxidative stress markers and its association with clinical outcomes in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention. Results: As indicated in the results, Post MI (Myocardial Infarction) heart failure was significantly higher in the group A (11 vs 4, p = 0.047). Complete STR (ST-segment resolution) was observed to be significantly higher in the group B (36 vs 17, p = 0.006). The SOD (Superoxide dismutase) and GPX (Glutathione peroxidase) levels were significantly higher in the group B compared to the other group (1547.51 ± 328.29 vs. 1449.97 ± 246.06, p = 0.019 and 60.62 ± 11.95 vs 57.41 ± 10.14, p = 0.042). The levels of GPX and SOD were shown to be directly related with complete STR and post PCI (Percutaneous coronary intervention)TIMI(Thrombolysis in Myocardial Infarction) flow 3 in the group A (p = 0.002 and p < 0.01, p = 0.005 and p < 0.02, respectively). © 2020, The Author(s)

Effects of Royal Jelly and Tocotrienol Rich Fraction in obesity treatment of calorie-restricted obese rats: A focus on white fat browning properties and thermogenic capacity

Background: Obesity has reached an alarming rate worldwide. Promoting thermogenesis via increasing the function of brown adipose tissue (BAT) or white adipose tissue (WAT) browning has been proposed as a new protective approach against obesity. The goal of this study was to evaluate the effects of Royal Jelly (RJ) and tocotrienol rich fraction (TRF) on BAT activation and WAT browning during calorie restriction diet (CRD) in obesity model. Methods: In this experimental study, 50 obese Wistar rats were randomly divided into 5 groups and then received one of the following treatments for a period of 8-week: High-fat diet (HFD), CRD, RJ + CRD, TRF + CRD, and RJ + TRF + CRD. Effects of RJ and TRF, individually and in combination on body weight and the expression of key thermoregulatory genes in WAT and BAT were examined by quantitative real-time (qRT-PCR). Also, morphological alterations were assessed by hematoxylin and eosin staining. Results: RJ (- 67.21 g ±4.84 g) and RJ + TRF (- 73.29 g ±4.51 g) significantly reduced weight gain relative to the CRD group (- 40.70 g ±6.50 g, P < 0.001). In comparison with the CRD group, RJ and RJ + TRF remarkably enhanced the uncoupling protein1 (UCP1) expression in WAT (5.81, 4.72 fold, P < 0.001) and BAT (4.99, 4.75 fold, P < 0.001). The expression of PR domain containing 16(PRDM 16), cAMP response element-binding protein1 (CREB1), P38 mitogen-activated protein kinases (P38MAPK), and Bone morphogenetic protein8B (BMP8B) have significantly increased following RJ and RJ + TRF treatments (P < 0.001). However, the expression levels of CCAAT/enhancer-binding protein beta (CEBPβ) and Bone morphogenetic protein7 (BMP7) did not remarkably change. Multilocular beige cells in WAT and compacted dense adipocytes were also observed in BAT of RJ and RJ + TRF received groups. TRF showed no substantial effects on the expression of the mentioned thermoregulatory genes and brown fat-like phenotype. Conclusion: Our results suggest that, Royal Jelly promotes thermogenesis and browning of WAT, contributing to an increase in energy expenditure. Thus, Royal Jelly may give rise to a novel dietary choice to attenuate obesity. © 2020 The Author(s)

Daily protein-polyphenol ingestion increases daily myofibrillar protein synthesis rates and promotes early muscle functional gains during resistance training

This is the final version. Available on open access from the American Physiological Society via the DOI in this recordFactors underpinning the time-course of resistance-type exercise training (RET) adaptations are not fully understood. The present study hypothesized that consuming a twice-daily protein-polyphenol beverage (PPB; n=15; age, 24 ± 1 years; BMI, 22.3 ± 0.7 kg·m-2) previously shown to accelerate recovery from muscle damage and increase daily myofibrillar protein synthesis (MyoPS) rates would accelerate early (10 sessions) improvements in muscle function and potentiate quadriceps volume and muscle fiber cross-sectional area (fCSA) following 30 unilateral RET sessions in healthy, recreationally active, adults. Versus isocaloric placebo (PLA; n=14; age, 25 ± 2 years; BMI, 23.9 ± 1.0 kg·m-2), PPB increased 48 h MyoPS rates after the first RET session measured using deuterated water (2.01 ± 0.15 %·d-1 vs. 1.51 ± 0.16 , respectively; P<0.05). Additionally, PPB increased isokinetic muscle function over 10 sessions of training relative to the untrained control leg (%U) from 99.9 ± 1.8 pre-training to 107.2 ± 2.4 %U at session 10 (versus 102.6 ± 3.9 to 100.8 ± 2.4 %U at session 10 in PLA; interaction P<0.05). Pre-to-post-training, PPB increased type II fCSA (PLA: 120.8 ± 8.2 to 109.5 ± 8.6 %U; PPB: 92.8 ± 6.2 to 108.4 ± 9.7 %U; interaction P<0.05), but the gain in quadriceps muscle volume was similar between groups. Similarly, PPB did not further increase peak isometric torque, muscle function or MyoPS measured post-training. This suggests that although PPB increases MyoPS and early adaptation, it may not influence longer term adaptations to unilateral RET.University of ExeterNational Institute of AgingNational Institute for Health Research (NIHR

On the Area Requirements of Planar Greedy Drawings of Triconnected Planar Graphs

In this paper we study the area requirements of planar greedy drawings of triconnected planar graphs. Cao, Strelzoff, and Sun exhibited a family $\cal H$ of subdivisions of triconnected plane graphs and claimed that every planar greedy drawing of the graphs in $\mathcal H$ respecting the prescribed plane embedding requires exponential area. However, we show that every $n$-vertex graph in $\cal H$ actually has a planar greedy drawing respecting the prescribed plane embedding on an $O(n)\times O(n)$ grid. This reopens the question whether triconnected planar graphs admit planar greedy drawings on a polynomial-size grid. Further, we provide evidence for a positive answer to the above question by proving that every $n$-vertex Halin graph admits a planar greedy drawing on an $O(n)\times O(n)$ grid. Both such results are obtained by actually constructing drawings that are convex and angle-monotone. Finally, we consider $\alpha$-Schnyder drawings, which are angle-monotone and hence greedy if $\alpha\leq 30^\circ$, and show that there exist planar triangulations for which every $\alpha$-Schnyder drawing with a fixed $\alpha<60^\circ$ requires exponential area for any resolution rule

Risk factors for delayed graft function in deceased donor kidney transplantation; A potential preventive role for intraoperative thymoglobulin

Introduction: Delayed graft function (DGF) is associated with significant adverse outcomes in deceased donor kidney transplantation (KT) including lower graft survival. However, risk factors and potential preventive strategies like intraoperative rabbit antithymocyte globulin (rATG; thymoglobulin) have not yet been fully evaluated. Objectives: The aim of this study was to investigate DGF risk factors and determine the association of intraoperative rATG with the risk of DGF in deceased donor kidney recipients. Patients and Methods: We retrospectively examined medical records of 163 first time deceased donor kidney transplant recipients at two major kidney transplant centers from 2014 to 2016. All the donors were standard heart-beating, brain death donors. Risk factors for DGF in recipients were evaluated using multivariate logistic regression analysis. Results: The mean recipients' age was 43±13 years and the majority of participants were male (64). The overall rate of DGF was 27. Intraoperative rATG was significantly associated with a lower rate of DGF (adjusted odds ratio AOR, 0.33, 95% CI, 0.11-0.95). Intraoperative transfusion (AOR, 3.7, 95% CI, 1.4-9.9) and diabetes mellitus (AOR, 3.7, 95% CI, 1.5-8.9) were significantly associated with higher risk of DGF. Conclusion: This study showed that intraoperative blood transfusion and diabetes mellitus were associated with increased risk of DGF. Meanwhile, administration of intraoperative rATG was associated with reduced odds ratio of DGF. Future studies are needed to evaluate the potential role of rATG in DGF-related renal outcomes. © 2019 The Author(s)

In vitro assessment of the combined effect of eicosapentaenoic acid, green tea extract and curcumin C3 on protein loss in C2C12 myotubes

EPA has been clinically shown to reduce muscle wasting during cancer cachexia. This study investigates whether curcumin or green tea extract (GTE) enhances the ability of low doses of eicosapentaenoic acid (EPA) to reduce loss of muscle protein in an in vitro model. A low dose of EPA with minimal anti-cachectic activity was chosen to evaluate any potential synergistic effect with curcumin or GTE. Depression of protein synthesis and increase in degradation was determined in C2C12 myotubes in response to tumour necrosis factor-α (TNF-α) and proteolysis-inducing factor (PIF). EPA (50 μM) or curcumin (10 μg ml−1) alone had little effect on protein degradation caused by PIF but the combination produced complete inhibition, as did the combination with GTE (10 μg ml−1). In response to TNF-α (25 ng ml−1)-induced protein degradation, EPA had a small, but not significant effect on protein degradation; however, when curcumin and GTE were combined with EPA, the effect was enhanced. EPA completely attenuated the depression of protein synthesis caused by TNF-α, but not that caused by PIF. The combination of EPA with curcumin produced a significant increase in protein synthesis to both agents. GTE alone or in combination with EPA had no effect on the depression of protein synthesis by TNF-α, but did significantly increase protein synthesis in PIF-treated cells. Both TNF-α and PIF significantly reduced myotube diameter from 17 to 13 μm for TNF-α (23.5%) and 15 μm (11.8%) for PIF However the triple combination of EPA, curcumin and GTE returned diameters to values not significantly different from the control. These results suggest that either curcumin or GTE or the combination could enhance the anti-catabolic effect of EPA on lean body mass

Effect of fenugreek (Trigonella foenum-graecum L.) intake on glycemia: A meta-analysis of clinical trials

10.1186/1475-2891-13-7Nutrition Journal131