Modular analysis of the probabilistic genetic interaction network

Motivation: Epistatic Miniarray Profiles (EMAP) has enabled the mapping of large-scale genetic interaction networks; however, the quantitative information gained from EMAP cannot be fully exploited since the data are usually interpreted as a discrete network based on an arbitrary hard threshold. To address such limitations, we adopted a mixture modeling procedure to construct a probabilistic genetic interaction network and then implemented a Bayesian approach to identify densely interacting modules in the probabilistic network

α-Linolenic Acid Inhibits RANKL-Induced Osteoclastogenesis In Vitro and Prevents Inflammation In Vivo

Inflammation is an important risk factor for bone-destroying diseases. Our preliminary research found that Zanthoxylum bungeanum seed oil (ZBSO) is abundant in unsaturated fatty acids and could inhibit osteoclastogenesis in receptor activator of nuclear factor κB ligand (RANKL)-induced RAW264.7 cells. However, the key constituents in ZBSO in the prevention of osteoclastogenesis and its possible mechanism related to inflammation are still unclear. Therefore, in this study, oleic acid (OA), linoleic acid (LA), palmitoleic acid (PLA), and alpha-linolenic acid (ALA) in ZBSO, havingthe strongest effect on RANKL-induced osteoclastogenesis, were selected by a tartrate-resistant acid phosphatase (TRAP) staining method. Furthermore, the effects of the selected fatty acids on anti-inflammation and anti-osteoclastogenesis in vitro and in vivo were assessed using RT-qPCR. Among the four major unsaturated fatty acids we tested, ALA displayed the strongest inhibitory effect on osteoclastogenesis. The increased expression of free fatty acid receptor 4 (FFAR4) and β-arrestin2 (βarr2), as well as the decreased expression of nuclear factor-kappa B (NF-κB), tumor necrosis factor-α (TNF-α), nuclear factor of activated T-cells c1 (NFATc1), and tartrate-resistant acid phosphatase (TRAP) in RAW264.7 cells after ALA treatment were observed. Moreover, in ovariectomized osteoporotic rats with ALA preventive intervention, we found that the expression of TNF-α, interleukin-6 (IL-6), interleukin-1β (IL-1β), NFATc1, and TRAP were decreased, while with the ALA therapeutic intervention, downregulated expression of NF-κB, NFATc1, TRAP, and transforming growth factor beta-activated kinase 1 (TAK1) were noticed. These results indicate that ALA, as the major unsaturated fatty acid in ZBSO, could inhibit RANKL-induced osteoclastogenesis via the FFAR4/βarr2 signaling pathway and could prevent inflammation, suggesting that ZBSO may be a promising potential natural product of unsaturated fatty acids and a dietary supplement for the prevention of osteoclastogenesis and inflammatory diseases

Multi‐technical analysis on the antioxidative capacity and total phenol contents of 94 traditional Chinese dietary medicinal herbs

Dietary medicinal herbs (DMHs) are superior reservoirs for natural antioxidants and safe for long‐term consumption. Chinese government recently announced an official list of traditional Chinese DMHs to support civil health promotion. However, antioxidative capacity (AOC) and total phenol contents (TPC) of these listed herbs were not comprehensively and systematically evaluated. In this study, AOC of 94 listed DMHs in water extract were investigated by three techniques including radical scavenging and ferric reducing antioxidative power. The results showed that emblic leafflower, rose, and clove possessed the highest AOC, while TPC was significantly correlated with AOC. While traditional Chinese medicines are categorized by the nature of Yin‐Yang, this study demonstrated that Yin DMHs are statistically correlated with high AOC. Practical application: In this study, AOC and TPC of 94 traditional Chinese DMHs were documented systematically. Emblic leafflower, rose and clove were shown to possess the highest AOC. TPC in traditional Chinese DMHs was significantly correlated with the AOC, while DMHs with Yin characteristic might be used as an indicator to identify potential antioxidative herbs

Separation and structural elucidation of a novel vardenafil analogue as an adulterant in a natural health care dietary supplement

A novel vardenafil analogue was identified in dietary supplement as an adulterant in herbal formulations. The structure of this analogue was elucidated using HRMS, NMR after extraction from the pulverized powder. It was named morphardenafil as a morpholine ring has replaced the N-ethyl piperazine ring in vardenafil. A tablet of this dietary supplement contained about 50 mg of unspecified morphardenafil, which is 2.5 – 20-times the prescriptive dosage of Levetra, the commercial formulation of the vardenafil monohydrochloride salt in the market and probably places unwary consumers at risk for potentially serious adverse effects or drug-drug interaction (DDI)