Though cardiovascular diseases (CVDs) and gastrointestinal disorders (GIDs) are different diseases associated with different organs, they are highly correlated clinically. Importantly, in Traditional Chinese Medicine (TCM), similar treatment strategies have been applied in both diseases. However, the etiological mechanisms underlying them remain unclear. Here, an integrated systems pharmacology approach is presented for illustrating the molecular correlations between CVDs and GIDs. Firstly, we identified pairs of genes that are associated with CVDs and GIDs and found that these genes are functionally related. Then, the association between 115 heart meridian (HM) herbs and 163 stomach meridian (SM) herbs and their combination application in Chinese patent medicine was investigated, implying that both CVDs and GIDs can be treated by the same strategy. Exemplified by a classical formula Sanhe Decoration (SHD) treating chronic gastritis, we applied systems-based analysis to introduce a drug-target-pathway-organ network that clarifies mechanisms of different diseases being treated by the same strategy. The results indicate that SHD regulated several pathological processes involved in both CVDs and GIDs. We experimentally confirmed the predictions implied by the effect of SHD for myocardial ischemia. The systems pharmacology suggests a novel integrated strategy for rational drug development for complex associated diseases.Over the past decade, there has been a marked increase in our understanding that there are higher prevalence rates of gastrointestinal disease (GIDs) in patients with cardiovascular disease (CVDs) 1,2 with similar dysfunctional phenotypes, such as rib pain, stomach pain, nausea and vomiting. However, the underlying co-occurrence mechanisms of CVDs and GIDs are unclear, thereby hampering development of drugs for both diseases in humans 3 . In modern Western medicine, usually, it has been observed that cardiovascular diseases have an etiological relationship with gastrointestinal disorders. Several studies have reported that the risk of cardiovascular disease in patients with gastrointestinal disease appears to be far greater than in the general population 4 . Moreover, some gastrointestinal disorders may increase patients' risk of cardiovascular disease as well. For example, patients with chronic gastrointestinal ischemia have an increased CVDs' risk and excess mortality 5 . Furthermore, the pathophysiological mechanisms between the two organs would supply realistic treatment for CVDs and GIDs 6 . For example, Iranian traditional physicians have introduced several remedies for heart-stomach association ailments in a previous study 7 . In addition, novel studies demonstrated the close relationship between gastroesophageal reflux disease (GERD) and the development of atrial fibrillation (AF), notably, acid-suppressive therapy is an effective strategy for the management of AF and may help to minimize the use of anti-arrhythmic agents 8,9 .

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Biological control using rhizosphere bacteria, Pseudomonas spp. and Serratia spp. is a prospective alternative technique to overcome plant parasitic nematodes infection. So, the current study was conducted in vitro on five egg-masses, 100 free eggs and 100 infective juveniles (IJs) of Meloidogyne incognita as well as greenhouse treatments on Luffa aegyptiaca L. to evaluate the nematicidal potential of six strains belong to Pseudomonas spp. and Serratia spp. as compared to oxamyl. Results showed that the inhibitory effect and juvenile mortality varied according to bacteria species, strains and exposure time. All the tested bacteria significantly ( P ≤ 0.05) inhibited egg hatching and increased juvenile mortality in vitro . After 3 days of treatment, Pseudomonas spp. were more effective against eggs (48.31to 55.15%) and IJs (20.98 to 25.30%) than Serratia spp. (44.55 to 49.75% with eggs) and (19.06 to 21.61% with IJs), respectively. In the pot experiment, Luffa aegyptiaca L. treated with Serratia spp. and Pseudomonas spp. displayed significantly higher ( P ≤ 0.05) levels of growth (as indicated by root length, fresh roots weight and fresh shoots weight) compared to control plants and significantly ( P ≤ 0.05) suppressed galling (number of galls) and reproduction (as indicated by number of egg-masses on roots and number of eggs and juveniles in pot soil). Meanwhile, among the treated plants, Serratia spp. and Pseudomonas spp. gave the best results in shoot weight of pots infected by eggs of M. incognita than those infected with IJs as compared with positive control. While, oxamyl treatment gave the best results in pots infected by eggs and IJs. The lowest galling (gall index), number of eggs and juveniles in soil was observed in the treatment with mixture of Serratia spp. and Pseudomonas spp. as well as, enhanced growth of sponge gourd more than application each of them alone. Pots treated with oxamyl overwhelmed those treated with mixture of Serratia spp. and Pseudomonas spp.

Drug target interactions (DTIs) are crucial in pharmacology and drug discovery. Presently, experimental determination of compound-protein interactions remains challenging because of funding investment and difficulties of purifying proteins. In this study, we proposed two in silico models based on support vector machine (SVM) and random forest (RF), using 1589 molecular descriptors and 1080 protein descriptors in 9948 ligand-protein pairs to predict DTIs that were quantified by K i values. The cross-validation coefficient of determination of 0.6079 for SVM and 0.6267 for RF were obtained, respectively. In addition, the two-dimensional (2D) autocorrelation, topological charge indices and three-dimensional (3D)-MoRSE descriptors of compounds, the autocorrelation descriptors and the amphiphilic pseudo-amino acid composition of protein are found most important for K i predictions. These models provide a new opportunity for the prediction of ligand-receptor interactions that will facilitate the target discovery and toxicity evaluation in drug development.

Background: Dengue virus (DENV) is an increasing global health threat and associated with induction of both a long-lived protective immune response and immune-suppression. So far, the potency of treatment of DENV via antiviral drugs is still under investigation. Recently, increasing evidences suggest the potential role of microRNAs (miRNAs) in regulating DENV. The present study focused on the function of miRNAs in innate insusceptible reactions and organization of various types of immune cells and inflammatory responses for DENV. Three drugs were tested including antiviral herbal medicine ReDuNing (RDN), Loratadine (LRD) and Acetaminophen. Results: By the microarray expression of miRNAs in 165 Patients. Results showed that 89 active miRNAs interacted with 499 potential target genes, during antiviral treatment throughout the critical stage of DENV. Interestingly, reduction of the illness threats using RDN combined with LRD treatment showed better results than Acetaminophen alone. The inhibitions of DENV was confirmed by decrease concentrations of cytokines and interleukin parameters; like TNF-α, IFN-γ, TGF-β1, IL-4, IL-6, IL-12, and IL-17; after treatment and some coagulants factors increased. Conclusions: This study showed a preliminary support to suggest that the herbal medicine RDN combined with LRD can reduce both susceptibility and the severity of DENV.