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For a given graph, the Grid Bandwidth Minimization Problem (GBMP) is to find an embedding of into a host graph such that the bandwidth over all edges is minimized. It is an NP-hard problem with applications in VLSI circuit design, numerical analysis, computational biology, graph theory and scheduling. In this paper, a Simulated Annealing (SA) algorithm is developed for GBMP in which initial solution is generated using two problem-specific construction heuristics. Four neighbourhood strategies are designed to explore the search space. Experiments conducted on benchmark instances achieve results which fall within the bounds whereas for grid graphs it attains optimal values. [ABSTRACT FROM AUTHOR]

Goals: To assess the efficacy and safety of Chinese Medicine Prescription “W-LHIT” in subjects with simple obesity, and to explore its potential mechanism of action. Methods: Thirty-seven patients aged 18 to 60 from Wei-En hospital (Weifang City, Shandong, China), participated in a double blinded, placebo-controlled study. Subjects were randomly divided into 2 groups, 18 in treatment and 19 in placebo group. The treatment group took the “W-LHIT” capsules for two months, while the control group received placebo capsules. Both groups accepted healthy lifestyle education materials. After a 2-month treatment, the placebo group transferred to open-label treatment after unblinding. Results: 72.22% participants in the treatment group lost more than 5% of their body weight, compared with 36.84% in the placebo group (p < 0.001). Body weight loss and body mass index reduction of the treatment group were also significantly higher than those of the placebo group (p < 0.05). These changes were accompanied by increased abundance of Akkermansia muciniphila and Enterococcus faecium, and decreased abundance of Proteobacteria in gut microbiota. Furthermore, the treatment group also showed improvement in obesity-related comorbidities such as hypertension and elevation of liver enzymes. No serious adverse reactions were found during the study period. Weight did not rebound at a follow-up visit 2 months after treatment. Conclusion: W-LHIT significantly improved body weight and comorbid conditions without obvious adverse reaction or rebound weight gain. These effects were associated with increased abundance of probiotics in gut microbiota. W-LHIT may have a potential for treating obesity in conjunction with healthy lifestyle modifications. [ABSTRACT FROM AUTHOR]

Introduction: Cytochrome P450 (CYP) 3A4 is a major drug metabolizing enzyme for corticosteroids (CS). Epimedium has been used for asthma and variety of inflammatory conditions with or without CS. It is unknown whether epimedium has an effect on CYP 3A4 and how it interacts with CS. We sought to determine the effects of epimedium on CYP3A4 and whether it affects the anti-inflammatory function of CS and identify the active compound responsible for this effect. Methods: The effect of epimedium on CYP3A4 activity was evaluated using the Vivid CYP high-throughput screening kit. CYP3A4 mRNA expression was determined in human hepatocyte carcinoma (HepG2) cells with or without epimedium, dexamethasone, rifampin, and ketoconazole. TNF-α levels were determined following co-culture of epimedium with dexamethasone in a murine macrophage cell line (Raw 264.7). Active compound (s) derived from epimedium were tested on IL-8 and TNF-α production with or without corticosteroid, on CYP3A4 function and binding affinity. Results: Epimedium inhibited CYP3A4 activity in a dose-dependent manner. Dexamethasone enhanced the expression of CYP3A4 mRNA, while epimedium inhibited the expression of CYP3A4 mRNA and further suppressed dexamethasone enhancement of CYP3A4 mRNA expression in HepG2 cells (p < 0.05). Epimedium and dexamethasone synergistically suppressed TNF-α production by RAW cells (p < 0.001). Eleven epimedium compounds were screened by TCMSP. Among the compounds identified and tested only kaempferol significantly inhibited IL-8 production in a dose dependent manner without any cell cytotoxicity (p < 0.01). Kaempferol in combination with dexamethasone showed complete elimination of TNF-α production (p < 0.001). Furthermore, kaempferol showed a dose dependent inhibition of CYP3A4 activity. Computer docking analysis showed that kaempferol significantly inhibited the catalytic activity of CYP3A4 with a binding affinity of −44.73kJ/mol. Discussion: Inhibition of CYP3A4 function by epimedium and its active compound kaempferol leads to enhancement of CS anti-inflammatory effect. [ABSTRACT FROM AUTHOR]

Nitric oxide (NO) and endothelin (ET) release from thrombin-treated rat aorta following vascular contraction were measured to determine the role of endothelin (ET) receptor-coupled NO release in thrombin-induced vascular reactivity. The results revealed production of NO after ET release and ET-1 receptor activation. Pretreatment with ET (sub B) receptor antagonists inhibited thrombin-induced NO release and the relaxation of precontracted aortic vessels. These results suggest a relationship between thrombin-induced ET-1 release and subsequent ET(sub B) receptor-coupled NO release, and vascular contractility.

Background: Excessive production of IgE plays a major role in the pathology of food allergy. In an attempt to identify anti‐IgE natural products, Arctium Lappa was one of the most effective herbs among approximately 300 screened medicinal herbs. However, little is known about its anti‐IgE compounds. Objective: To identify compounds from Arctium Lappa for targeted therapy on IgE production and explore their underlying mechanisms. Methods: Liquid‐liquid extraction and column chromatographic methods were used to purify the compounds. IgE inhibitory effects were determined on IgE‐producing human myeloma U266 cells, peanut‐allergic murine model and PBMCs from food‐allergic patients. Genes involved in IgE inhibition in PBMCs were studied by RNA sequencing. Results: The main compounds isolated were identified as arctiin and arctigenin. Both compounds significantly inhibited IgE production in U266 cells, with arctigenin the most potent (IC50=5.09μg/mL). Arctigenin (at a dose of 13 mg/kg) markedly reduced peanut‐specific IgE levels, blocked hypothermia and histamine release in a peanut‐allergic mouse model. Arctigenin also significantly reduced IgE production and Th2 cytokines (IL‐5, IL‐13) by PBMCs. We found 479 differentially expressed genes in PBMCs with arctigenin treatment (p <.001 and fold‑change ≥1.5), involving 24 gene ontology terms (p <.001, FDR <0.05); cell division was the most significant. Eleven genes including UBE2C and BCL6 were validated by qPCR. Conclusion: Arctigenin markedly inhibited IgE production in U266 cells, peanut‐allergic murine model and PBMCs from allergic patients by down‐regulating cell division, cell cycle‐related genes and up‐regulating anti‐inflammatory factors. [ABSTRACT FROM AUTHOR]