Herb Target Prediction Based on Representation Learning of Symptom related Heterogeneous Network.

Traditional Chinese Medicine (TCM) has received increasing attention as a complementary approach or alternative to modern medicine. However, experimental methods for identifying novel targets of TCM herbs heavily relied on the current available herb-compound-target relationships. In this work, we present an Herb-Target Interaction Network (HTINet) approach, a novel network integration pipeline for herb-target prediction mainly relying on the symptom related associations. HTINet focuses on capturing the low-dimensional feature vectors for both herbs and proteins by network embedding, which incorporate the topological properties of nodes across multi-layered heterogeneous network, and then performs supervised learning based on these low-dimensional feature representations. HTINet obtains performance improvement over a well-established random walk based herb-target prediction method. Furthermore, we have manually validated several predicted herb-target interactions from independent literatures. These results indicate that HTINet can be used to integrate heterogeneous information to predict novel herb-target interactions

Unpacking constructs: a network approach for studying war exposure, daily stressors and post-traumatic stress disorder

Conflict affected populations are exposed to stressful events during and after war, and it is well established that both take a substantial toll on individuals' mental health. Exactly how exposure to events during and after war affect mental health is a topic of considerable debate. Various hypotheses have been put forward on the relation between stressful war exposure (SWE), daily stressors (DS) and the development of post-traumatic stress disorder (PTSD). This paper seeks to contribute to this debate by critically reflecting upon conventional modeling approaches and by advancing an alternative model to studying interrelationships between SWE, DS, and PTSD variables. The network model is proposed as an innovative and comprehensive modeling approach in the field of mental health in the context of war. It involves a conceptualization and representation of variables and relationships that better approach reality, hence improving methodological rigor. It also promises utility in programming and delivering mental health support for war-affected populations

Elucidation of the mechanisms and molecular targets of Yiqi Shexue formula for treatment of primary immune thrombocytopenia based on network pharmacology

Yiqi Shexue formula (YQSX) is traditionally used to treat primary immune thrombocytopenia (ITP) in clinical practice of traditional Chinese medicine. However, its mechanisms of action and molecular targets for treatment of ITP are not clear. The active compounds of YQSX were collected and their targets were identified. ITP-related targets were obtained by analyzing the differential expressed genes between ITP patients and healthy individuals. Protein-protein interaction (PPI) data were then obtained and PPI networks of YQSX putative targets and ITP-related targets were visualized and merged to identify the candidate targets for YQSX against ITP. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis were carried out. The gene-pathway network was constructed to screen the key target genes. In total, 177 active compounds and 251 targets of YQSX were identified. Two hundred and thirty differential expressed genes with an P value 1 were identified between ITP patient and control groups. One hundred and eighty-three target genes associated with ITP were finally identified. The functional annotations of target genes were found to be related to transcription, cytosol, protein binding, and so on. Twenty-four pathways including cell cycle, estrogen signaling pathway, and MAPK signaling pathway were significantly enriched. MDM2 was the core gene and other several genes including TP53, MAPK1, CDKN1A, MYC, and DDX5 were the key gens in the gene-pathway network of YQSX for treatment of ITP. The results indicated that YQSX's effects against ITP may relate to regulation of immunological function through the specific biological processes and the related pathways. This study demonstrates the application of network pharmacology in evaluating mechanisms of action and molecular targets of complex herbal formulations

Network-Based Pharmacology Study Reveals Protein Targets for Medical Benefits and Harms of Cannabinoids in Humans

This network-based pharmacology study intends to uncover the underlying mechanisms of cannabis leading to a therapeutic benefit and the pathogenesis for a wide range of diseases claimed to benefit from or be caused by the use of the cannabis plant. Cannabis contains more than 600 chemical components. Among these components, cannabinoids are well-known to have multifarious pharmacological activities. In this work, twelve cannabinoids were selected as active compounds through text mining and drug-like properties screening and used for initial protein-target prediction. The disease-associated biological functions and pathways were enriched through GO and KEGG databases. Various biological networks [i.e., protein-protein interaction, target-pathway, pathway-disease, and target-(pathway)-target interaction] were constructed, and the functional modules and essential protein targets were elucidated through the topological analyses of the networks. Our study revealed that eighteen proteins (CAT, COMT, CYP17A1, GSTA2, GSTM3, GSTP1, HMOX1, AKT1, CASP9, PLCG1, PRKCA, PRKCB, CYCS, TNF, CNR1, CNR2, CREB1, GRIN2B) are essential targets of eight cannabinoids (CBD, CBDA, Delta(9)-THC, CBN, CBC, CBGA, CBG, Delta(8)-THC), which involve in a variety of pathways resulting in beneficial and adverse effects on the human body. The molecular docking simulation confirmed that these eight cannabinoids bind to their corresponding protein targets with high binding affinities. This study generates a verifiable hypothesis of medical benefits and harms of key cannabinoids with a model which consists of multiple components, multiple targets, and multiple pathways, which provides an important foundation for further deployment of preclinical and clinical studies of cannabis

Does area type matter for pedestrian distribution? Testing movement economy theory on gated and non-gated housing estates in Wuhan, China

This study investigates how the built environment influences pedestrian distribution in housing estates and whether its influence differs between gated and non-gated housing types. This study is built upon the theoretical framework of the movement economy, initially proposed by scholars from the Space Syntax Laboratory and recently extended by others. The extended movement economy framework conceptualises the interrelationship between street configuration, functional uses, physical structures, and pedestrian movement. To evaluate the hypothesised associations within this theoretical framework, we constructed structural equation modelling using pedestrian movement data of 606 locations from six pairs of gated and non-gated housing estates in Wuhan, China. We assessed the direct, indirect, and total effects of street configuration, functional uses, and physical structures on pedestrian movement. We then conducted a multigroup analysis to determine whether statistically significant differences exist between gated and non-gated housing areas regarding how the three spatial factors affect pedestrian movement. The findings indicated that the structural model could explain over 60 % of variances on pedestrian movement data, regardless of housing types. Although pedestrian movement demonstrated statistically significant correlations with street configuration, functional use, and physical structure, the street configuration was the most powerful and reliable predictor of all. This paper also evidenced that functional use and physical structure were two effective mediators between street configuration and pedestrian movement, albeit with small mediating effect sizes. More importantly, the results also uncovered several statistically significant differences in the builtenvironmental influences between gated and non-gated models. To the best of our knowledge, this is the first study that (i) verifies the direct, indirect, and total effects of the built environment on pedestrian movement in Chinese housing estates; and (ii) confirms statistically significant differences between gated and non-gated housing types in their built-environmental impacts on pedestrian movement

Conceptualised psycho-medical footprint for health status outcomes and the potential impacts for early detection and prevention of chronic diseases in the context of 3P medicine

Background: The Suboptimal Health Status Questionnaire-25 (SHSQ-25) is a distinctive medical psychometric diagnostic tool designed for the early detection of chronic diseases. However, the synaptic connections between the 25 symptomatic items and their relevance in supporting the monitoring of suboptimal health outcomes, which are precursors for chronic diseases, have not been thoroughly evaluated within the framework of predictive, preventive, and personalised medicine (PPPM/3PM). This baseline study explores the internal structure of the SHSQ-25 and demonstrates its discriminatory power to predict optimal and suboptimal health status (SHS) and develop photogenic representations of their distinct relationship patterns. Methods: The cross-sectional study involved healthy Ghanaian participants (n = 217; aged 30–80 years; ~ 61% female), who responded to the SHSQ-25. The median SHS score was used to categorise the population into optimal and SHS. Graphical LASSO model and multi-dimensional scaling configuration methods were employed to describe the network structures for the two populations. Results: We observed differences in the structural, node placement and node distance of the synaptic networks for the optimal and suboptimal populations. A statistically significant variance in connectivity levels was noted between the optimal (58 non-zero edges) and suboptimal (43 non-zero edges) networks (p = 0.024). Fatigue emerged as a prominently central subclinical condition within the suboptimal population, whilst the cardiovascular system domain had the greatest relevance for the optimal population. The contrast in connectivity levels and the divergent prominence of specific subclinical conditions across domain networks shed light on potential health distinctions. Conclusions: We have demonstrated the feasibility of creating dynamic visualizers of the evolutionary trends in the relationships between the domains of SHSQ-25 relative to health status outcomes. This will provide in-depth comprehension of the conceptual model to inform personalised strategies to circumvent SHS. Additionally, the findings have implications for both health care and disease prevention because at-risk individuals can be predicted and prioritised for monitoring, and targeted intervention can begin before their symptoms reach an irreversible stage. We observed differences in the structural, node placement and node distance of the synaptic networks for the optimal and suboptimal populations. A statistically significant variance in connectivity levels was noted between the optimal (58 non-zero edges) and suboptimal (43 non-zero edges) networks (p = 0.024). Fatigue emerged as a prominently central subclinical condition within the suboptimal population, whilst the cardiovascular system domain had the greatest relevance for the optimal population. The contrast in connectivity levels and the divergent prominence of specific subclinical conditions across domain networks shed light on potential health distinctions