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The therapeutic efficacy of Danshen and Jiangxiang in the treatment of ischemic stroke (IS) is relatively significant. Studying the mechanism of action of Danshen and Jiangxiang in the treatment of IS can effectively identify candidate traditional Chinese medicines (TCM) with efficacy. However, it is challenging to analyze the effector substances and explain the mechanism of action of Danshen-Jiangxiang from a systematic perspective using traditional pharmacological approaches. In this study, a systematic study was conducted based on the drug-target-symptom-disease association network using complex network theory. On the basis of the association information about Danshen, Jiangxiang and IS, the protein-protein interaction (PPI) network and the "drug pair-pharmacodynamic ingredient-target-IS" network were constructed. The different topological features of the networks were analyzed to identify the core pharmacodynamic ingredients including formononetin in Jiangxiang, cryptotanshinone and tanshinone IIA in Danshen as well as core target proteins such as prostaglandin G/H synthase 2, retinoic acid receptor RXR-alpha, sodium channel protein type 5 subunit alpha, prostaglandin G/H synthase 1 and beta-2 adrenergic receptor. Further, a method for screening IS candidates based on TCM symptoms was proposed to identify key TCM symptoms and syndromes using the "drug pair-TCM symptom-syndrome-IS" network. The results showed that three TCMs, namely Puhuang, Sanleng and Zelan, might be potential therapeutic candidates for IS, which provided a theoretical reference for the development of drugs for the treatment of IS.
Subject(s)
Ischemic Stroke , Salvia miltiorrhiza , Stroke/drug therapy , Cyclooxygenase 2 , ProstaglandinsABSTRACT
ObjectiveTo explore the "efficacy-toxicity" association mechanisms of Tripterygium wilfordii polyglycoside tablets （TWPT） by establishing and analyzing an interaction network associated with the clinical efficacy of TWPT in the treatment of rheumatoid arthritis （RA） and TWPT-induced liver injury. MethodOn the basis of the TWPT efficacy-related gene expression profile and TWPT-induced liver injury-related protein expression profile which were both obtained from our clinical cohorts， the "efficacy-toxicity" association network of TWPT was constructed， and the key network targets were identified by calculating the topological values of the nodes， including the degree， closeness and betweenness. After that， the biological functions and pathways of the key network targets were investigated by enrichment analysis. ResultA total of 119 differentially expressed genes （58 up-regulated and 61 down-regulated） between RA patients with TWPT well and weak response were identified as TWPT efficacy-related genes by clinical transcriptomics， and 49 differentially expressed proteins （36 up-regulated and 13 down-regulated） were demonstrated to be TWPT-induced liver injury-related proteins by clinical proteomics. In addition， the clinical symptom enrichment analysis indicated that the TWPT efficacy-related genes were significantly associated with various clinical symptoms of arthralgia in traditional Chinese medicine and clinical phenotypes of modern medicine， and most of the TWPT-induced liver injury-related proteins were involved in digestive system abnormalities. Therefore， the aforementioned multi-omics data represented the main clinical symptoms of TWPT treating RA and inducing liver injury. Mechanically， the "efficacy-toxicity" association network revealed that both TWPT efficacy-related genes and TWPT-induced liver injury-related core proteins were involved in the "immune-inflammatory" imbalance， especially playing an important role in neutrophil degranulation， complement cascade reaction， and immune-inflammatory response mediated by protein post-translational modification. Notably， the above genes and proteins were also enriched in various signaling pathways related to cell proliferation and cell cycle regulation， such as RAS and mitogen-activated protein kinase （MAPK） signaling pathway， and in several liver functional processes， such as glycogen metabolism and redox reaction. ConclusionThis study systematically explained the "efficacy-toxicity" association characteristics and molecular mechanisms of TWPT by applying a research strategy integrating clinical phenomics， transcriptomics and proteomics， laying a good data foundation for exploring the "efficacy enhancing and toxicity-reducing" mechanisms of TWPT.
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Growing clinical evidence shows that Qufeng Gutong Cataplasm may exert a significant analgesic effect. However, the pharmacological characteristics and mechanisms underlying this prescription are still unclear. In the current study, a "disease-syndrome-symptom-formula" association network analysis was performed to explore the pharmacological characteristics and mechanisms of Qufeng Gutong Cataplasm against osteoarthritis (OA), neuropathic pain (NP), chronic inflammatory pain (CIP) and myofascial pain syndrome (MPS) by integrating clinical phenomics data, transcriptomics data and biological interaction network mining. As a result, the three functional modules (Qufeng Sanhan-QFSHG, Shujin Huoxue-SJHXG and Xiaozhong Zhitong-XZZTG) enriched by the drug network targets were all related to the pharmacological effects of Qufeng Gutong Cataplasm, including dispersing cold and relieving pain, activating blood and relieving pain, reducing swelling and relieving pain. In addition, the main pharmacological effects of QFSHG and XZZTG were dispelling wind and dispersing cold and dehumidifying, promoting Qi and reducing swelling and relieving pain, respectively. In terms of reversing the imbalance of "immune-inflammation-vascular axis", the main pharmacological effects of SJHXG were regulating the liver and promoting Qi, activating blood circulation and removing stasis. Mechanically, the key network targets of Qufeng Gutong Cataplasm against OA, NP, CIP and MPS may play a therapeutic role in relieving hyperalgesia and paresthesia by reversing the "neuro-endocrine-immune" imbalance system during the occurrence and progression of diseases. In conclusion, our data indicate that Qufeng Gutong Cataplasm may relieve the pain and wind-cold-dampness arthralgia syndrome related symptoms by regulating the "neuro-endocrine-immune" system, neurological and endocrine disorders and reversing the imbalance of "immunity-inflammation". The relevant results may provide a network-based evidence for clinical positioning of Qufeng Gutong Cataplasm, and offer a direction for further clinical and experimental validation.
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The present study explored the biological connotation of traditional Chinese medicine(TCM) syndromes of rheumatoid arthritis(RA) from the "disease-syndrome-symptom" association network. RA patients with four TCM syndromes(dampness-heat obstruction, phlegm-stasis obstruction, Qi-blood deficiency, and liver and kidney deficiency), three for each type, were assigned as the RA TCM syndrome group, and three healthy volunteers as the normal control group. The differential gene sets of four syndromes were screened out through transcriptome expression profiling and bioinformatics mining. The relevant gene sets of syndrome-related clinical symptoms were collected from TCMIP v2.0(http://www.tcmip.cn/). The "disease-syndrome-symptom" association networks of four RA syndromes were established by using the intersection genes of syndrome-related differential genes and symptom-related genes, and the key network target genes of each syndrome were screened out and the corresponding biological functions were mined through topological feature calculation and enrichment analysis. The genes associated with clinical symptoms such as vasculitis, joint pain, and fever in the damp-heat obstruction syndrome ranked the top, and the key network target genes of this syndrome were most significantly enriched in the pathways related to material and energy metabolism and thermal reaction biological processes. The clinical symptom-related genes of the phlegm-stasis obstruction syndrome were most significantly enriched in the pathways related to "immunity-inflammation", nervous system regulation, and sensory response. The clinical symptoms such as hypoglycemia, hypotension, weight loss, palpitation, and arrhythmia in Qi-blood deficiency syndrome were predominant, and its key network target genes were most significantly enriched in the pathways related to the nervous system and "immunity-inflammation" response. The abnormal symptoms in the liver and kidney in the liver and kidney deficiency syndrome were commonly seen, and its key network target genes were most significantly enriched in the "immunity-inflammation" regulatory pathways, and liver and kidney development and metabolic response. In conclusion, the differences and connections of the biological basis between different TCM syndromes of RA are in line with the theoretical interpretation of TCM on the etiology and pathogenesis of RA. This study summarized the objective essence of syndromes to a certain extent from the "disease-syndrome-symptom" association network and is expected to provide a theoretical basis for the discovery of serum biomarkers of RA syndromes.
Subject(s)
Humans , Arthritis, Rheumatoid/genetics , Hot Temperature , Kidney , Medicine, Chinese Traditional , SyndromeABSTRACT
Over the past decade, traditional Chinese medicine (TCM) has widely embraced systems biology and its various data integration approaches to promote its modernization. Thus, integrative pharmacology-based traditional Chinese medicine (TCMIP) was proposed as a paradigm shift in TCM. This review focuses on the presentation of this novel concept and the main research contents, methodologies and applications of TCMIP. First, TCMIP is an interdisciplinary science that can establish qualitative and quantitative pharmacokinetics-pharmacodynamics (PK-PD) correlations through the integration of knowledge from multiple disciplines and techniques and from different PK-PD processes
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Background: Diabetes epidemic is an evolving phenomenon in Nigeria and sub-Saharan Africa. Most African governments are showing strong desire to reversing the current trend. However, information on the perception and readiness of rural and suburban community dwellers towards managing this disease need to be gathered.Methods: This was mixed methods including descriptive observational study and survey regarding establishment of a diabetic network in the rural and suburban localities. Quantitative screening data were collected to assess prevalence of diabetes or prediabetes, as well as investigate the perceptions of diabetic and non-diabetic residents. Establishment of diabetes register was initiated. 180 complete questionnaires were included for analysis, though 199 consented to participate. In the qualitative phase of the research, a convenience sampling questionnaire and focus group discussion on their perception about diabetes association or network. Their perceived response and opinions were then documented.Results: Among the participants, approximately 12% prevalence of diabetes and 10% prediabetes were observed. 19/25 cases of diabetes were entered in the register. Over 43% of the population never heard about diabetes association/network, but 72% of the diabetes cohort are willing to join diabetes network. A greater fraction of the suburban patients seems more aware, but willingness to accept diabetes is higher in the rural community.Conclusions: Most of the persons living with diabetes, and their relatives, are willingly to join diabetes network as well as encourage such organisation in their communities. Given the level of unawareness, there is need to establish diabetic association and advance the benefits.
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A dramatic increase in large-scale cross-sectional and temporal-level metagenomic experiments has led to an improvedunderstanding of the microbiome and its role in human well-being. Consequently, a plethora of analytical methods has beendeveloped to decipher microbial biomarkers for various diseases, cluster different ecosystems based on microbial content,and infer functional potential of the microbiome as well as analyze its temporal behavior. Development of user-friendlyvisualization methods and frameworks is necessary to analyze this data and infer taxonomic and functional patternscorresponding to a phenotype. Thus, new methods as well as application of pre-existing ones has gained importance inrecent times pertaining to the huge volume of the generated microbiome data. In this review, we present a brief overview ofsome useful visualization techniques that have significantly enriched microbiome data analytics.