The BP-M* Methodology for Process Analysis in the Health Sector

In this paper we present the main phases of the BP-M* methodology and its application to a care pathway for patients in the Oncology Division of a large hospital, to evaluate pros and cons of different drug administration modalities and the impact of these modalities to the organizational process. BP-M* has been developed for the manufacturing sector but the relevance of business modeling, analysis and reorganization is not restricted to a specific sector. The aim of this work is to show its application to a real life study of a complex process in the health sector.

Mechanistic insights toward identification and interaction of plant parasitic nematodes:A review

Nematode identification serves as an important param-eter to study their behaviour,importance and pathogenic-ity.Application of classical morphometric based identifica-tion methods prove to be lacking due to insufficient knowledge on morphological variations among closely related taxa.Molecular approaches such as DNA and protein-based information,microarray,probing,sequence-based methods and others have been used to supplement morphology-based methods for nematode identification.Ascarosides and certain protein-based nematode-associated molecular patterns(NAMPs),can be perceived by the host plants,and can initiate a signalling cascade.This review primarily emphasizes on an updated account of different classical and modern tools used for the identification of nematodes.Besides we also summa-rize the mechanism of some important signalling pathways which are involved in the different plant nematode interactions.Nematodes constitute most diverse and least studied group of soil inhabiting invertebrates.They are ecologically and physiologically important,however,wide range of nematodes show harmful impact on the individuals that live within their vicinity.Plant parasitic nematodes(PPNs)are transparent,pseudocoelomate,free living or parasitic microorganisms.PPNs lack morphometric identification methods due to insufficient knowl-edge on morphological variations among closely related taxa.As such,molecular approaches such as DNA and protein-based information,microarray,probing,sequence-based methods and others have been used to supplement morphology-based methods for their identification.To invade the defense response of different plant species,parasitic nematodes have evolved different molecular strategies.Ascarosides and certain protein-based nematode-associated molecular patterns(NAMPs),can be perceived by the host plants,and can initiate a signaling cascade.To overcome the host confrontation and develop certain nematode feeding sites,some members can inject effectors into the cells of susceptible hosts to reprogram the basal resistance signaling.This review primarily emphasizes on an updated account of different classical and modem tools used for the identification of PPNs.Besides we also summarize the mechanism of some important signaling pathways which are involved in the different plant nematode interactions.

Anti-inflammatory germacrane-type sesquiterpene lactones from Vernonia sylvatica

Nine new germacranolides,sylvaticalides A−H(1-9),and three known analogues(10-12)were isolated from the aeri-al part of Vernonia sylvatica.Their structures were established using comprehensive spectroscopic analysis,including high-resolution electrospray ionization mass spectroscopy(HR-ESI-MS)and 1D and 2D nuclear magnetic resonance(NMR)spectra.Their absolute configurations were determined by X-ray diffraction experiments.The anti-inflammatory activities of all isolated compounds were as-sessed by evaluating their inhibitory effects on the nuclear factor kappa B(NF-κB)pathway,which was activated by lipopolysacchar-ide(LPS)-stimulated human THP1-Dual cells,and the interferon-stimulated gene(ISG)pathway,activated by STING agonist MSA-2 in the same cell model.Compounds 1,2 and 6 showed inhibitory effects on the NF-κB and ISG signaling pathways,with IC_(50)values ranging from 4.12 to 10.57μmol·L^(−1).

HISP： a hybrid intelligent approach for identifying Jirected signaling pathways

Signal transduction plays important roles in biological systems. Unfortunately, our knowledge about signaling pathways is far from complete. Specifically, the direction of signaling flows is less known even though the signaling molecules of some signaling pathways have been determined. In this paper, we propose a novel hybrid intelligent method, namely HISP （Hybrid Intelligent approach for identifying directed Signaling Pathways）, to determine both the topologies of signaling pathways and the direction of signaling flows within a pathway based on integer linear programming and genetic algorithm. By integrating the protein-protein interaction, gene expression, and gene knockout data, our HISP approach is able to determine the optimal topologies of signaling pathways in an accurate way. Benchmark results on yeast MAPK signaling pathways demonstrate the efficiency of our proposed approach. When applied to the EGFR/ErbB signaling pathway in human hepatocytes, HISP unveils a high-resolution signaling path- way, where many signaling interactions were missing by existing computational approaches.

Effects of extracts from soothing-liver and invigorating-spleen formulas on the injury induced by oxidative stress in the hepatocytes of rats with non-alcoholic fatty liver disease induced by high-fat diet

OBJECTIVE:To investigate effects of the extracts from soothing-liver and invigorating-spleen formulas on the injury due to oxidative stress,mediated by the Nuclear factor-like 2(Nrf2)-Antioxidant response element(ARE) pathway,in the hepatocytes of rats with non-alcoholic fatty liver disease(NAFLD) induced by high-fat diet.METHODS:Soothing-liver and invigorating-spleen formula mixtures were prepared for five groups:normal,model,soothing-liver formula group(SLG),invigorating-spleen formula group(ISG),integrated formula group(IG).The rat model of NAFLD was induced by feeding rats a high-fat diet(HFD).After 16 weeks,the hepatic tissue was examined following Haematoxylin-Eosin(H&E) staining and with Transmission electron microscopy(TEM).Levels of hepatic lipids,serum lipids and hepatic functions were measured using a biochemical analyser.Hepatocytes were isolated from the livers of rats and were identified by cellar immunohistochemistry,cellular immunofluorescence and flow cytometry.The expression levels of Nrf2,Kelch-like epichlorohydrin-associated protein 1(Keap-1),haeme oxygenase-1(HO-1) and NAD(P)H:quinone oxidoreductase 1(NQO1) m RNAs were assessed by real-time fluorescence quantitative PCR.Nrf2,Keap-1,HO-1 and NQO1 proteins were measured by Western blotting.Finally,the levels of oxidative stress factors Superoxide Dismutase(SOD),malonaldehyde(MDA) and Glutathione peroxidase(GSH-Px) in hepatocytes were measured by WST-1,TBA and colorimetry.RESULTS:The H & E and TEM results showed that the NAFLD model rats successfully reproduced typical pathogenetic and histopathological features.The liver function and levels of hepatic lipids and serum lipids from the model rats were dramatically increased.Compared with the model group,the levels of hepatic lipids,serum lipids and hepatic function in the treatment groups were ameliorated to different degrees.The yields of purified hepatocytes in each rat were 4-5 × 108.The viability of the isolated hepatocytes was higher than 95%,with a purity over 93.2%.Cellular immunohistochemistry analysis showed that the hepatocytes were brown,while in the cellular immunofluorescence analysis,the hepatocytes showed green fluorescence.The expression levels of Nrf2,Keap-1,HO-1 and NQO1 m RNA and protein in the hepatocytes were significantly higher in the model group than in the normal group(P < 0.05,P < 0.01).Compared with the model group,the expression of Nrf2,Keap-1,HO-1 and NQO-1 m RNAs and proteins in all treatment groups increased,especially in the IG(P < 0.01).CONCLUSION:The extracts from soothing-liver and invigorating-spleen formulas may protect the liver against the injury induced by oxidative stress in hepatocytes by influencing the Nrf2-ARE pathway,which may be the mechanism having the potential for prevention and treatment of NAFLD.