Predicting new molecular targets for rhein using network pharmacology

<p>Abstract</p> <p>Background</p> <p>Drugs can influence the whole biological system by targeting interaction reactions. The existence of interactions between drugs and network reactions suggests a potential way to discover targets. The in silico prediction of potential interactions between drugs and target proteins is of core importance for the identification of new drugs or novel targets for existing drugs. However, only a tiny portion of drug-targets in current datasets are validated interactions. This motivates the need for developing computational methods that predict true interaction pairs with high accuracy. Currently, network pharmacology has used in identifying potential drug targets to predicting the spread of drug activity and greatly contributed toward the analysis of biological systems on a much larger scale than ever before.</p> <p>Methods</p> <p>In this article, we present a computational method to predict targets for rhein by exploring drug-reaction interactions. We have implemented a computational platform that integrates pathway, protein-protein interaction, differentially expressed genome and literature mining data to result in comprehensive networks for drug-target interaction. We used Cytoscape software for prediction rhein-target interactions, to facilitate the drug discovery pipeline.</p> <p>Results</p> <p>Results showed that 3 differentially expressed genes confirmed by Cytoscape as the central nodes of the complicated interaction network (99 nodes, 153 edges). Of note, we further observed that the identified targets were found to encompass a variety of biological processes related to immunity, cellular apoptosis, transport, signal transduction, cell growth and proliferation and metabolism.</p> <p>Conclusions</p> <p>Our findings demonstrate that network pharmacology can not only speed the wide identification of drug targets but also find new applications for the existing drugs. It also implies the significant contribution of network pharmacology to predict drug targets.</p

In vitro culture method of powdery mildew (Oidium heveae Steinmann) of Hevea brasiliensis

A method for culturing powdery mildew (Oidium heveae) from isolated leaves of Hevea brasiliensis was evaluated, which included three steps: Leaves and fungi selection, nutrient solution and culture dish  preparation, fungi inoculation and culture. The culture time and produced conidia number were considered as decision index. We tested the influence of micro components of nutrient solution including 6-benzylaminopurine (6-BA), salicylic acid (SA) and vitamin C (VC) and evaluated the culture difference of various leaf phenological phases and rubber tree clones. The results show that the longest culture time of isolated leaves emerged on modified Murashige and Skoog (MS) macro elements with 4 mg/L 6-BA, 20 mg/L SA, 1 mg/L VC. The colour phase leaf was the preferable choice for culturing average 15 to 16 days and producing 3.2222 × 106 mL-1 conidia. The culture effects of using various rubber clones were different and higher resistance clones cultured less conidia. The method leading to mass production of powdery mildew was simple using a climate incubator to resolve problems linked to season and space limitation and preservation of powdery mildew. This method could improve rubber resistance breeding process.Key words: Hevea brasiliensis, Oidium heveae, in vitro culture, nutrient solution, phenological phase

Characterization of Conserved Combined T and B Cell Epitopes in Leptospira interrogans Major Outer Membrane Proteins OmpL1 and LipL41

<p>Abstract</p> <p>Background</p> <p><it>Leptospira interrogans </it>are bacterial pathogens of animal that cause zoonotic infections in human. Outer membrane proteins of leptospire are among the most effective antigens which can stimulate remarkable immune responses during the infection processes, and thus are currently considered leading candidate vaccine antigens. The objective of the present study is to predict and confirm major combined B and T cell epitopes of leptospiral outer membrane proteins OmpL1 and LipL41, as well as to evaluate their capacity in the induction of immune responses in BALB/c mice.</p> <p>Results</p> <p>In this study, four epitopes from OmpL1 and four from LipL41 conserved regions were evaluated for their potential utilization in leptospire vaccines. Firstly, combined B and T cell epitopes were predicted by softwares and expressed using a phage display system. OmpL1 residues 87-98 and 173-191 (OmpL1_87-98and OmpL1_173-191) and LipL41_30-48, LipL41_233-256of LipL41 were identified as immunodominant B cell epitopes by Western blot. Epitopes OmpL1_173-191, OmpL1_297-320of OmpL1 and LipL41_233-256, LipL41_263-282of LipL41 were identified as immunodominant CD4⁺T cell epitopes through proliferation analysis of splenocytes from recombinant OmpL1 (rOmpL1) or recombinant LipL41 (rLipL41)-immunized BALB/c (H-2^d) mice. These epitopes induced responses of CD4⁺T cells and Th1 (T helper cells) type cytokine responses during the infection.</p> <p>Conclusion</p> <p>This work identified combined T and B cell immunodominant epitopes in outer membrane proteins OmpL1 and LipL41 of <it>Leptospira interrogans</it>. OmpL1_173-191of OmpL1 and LipL41_233-256of LipL41 could be useful in a vaccine against <it>Leptospira</it>. The findings could also contribute to the development of effective cross-protective vaccine strategies for leptospirosis.</p

Development of a Verification Technique for On-wafer Noise Figure Measurement Systems

We present the development of a verification technique for on-wafer noise figure (NF) measurement systems. As the key element of the technique, a verification device consisting of a mismatched attenuator and a low noise amplifier (LNA) has been developed. The attenuator and the LNA are fabricated on two separate chips but joined with a bondwire. The verification procedure based on the device has also been developed and tested on an on-wafer vector network analyzer system with a noise measurement option across the frequency range from 2 GHz to 20 GHz. It has also been found that the bondwire contributes to negligible effect on the system when NF is high e.g. 3 dB but slightly higher when NF is smaller e.g. 1 dB

Intelligent ZHENG Classification of Hypertension Depending on ML-kNN and Information Fusion

Hypertension is one of the major causes of heart cerebrovascular diseases. With a good accumulation of hypertension clinical data on hand, research on hypertension's ZHENG differentiation is an important and attractive topic, as Traditional Chinese Medicine (TCM) lies primarily in “treatment based on ZHENG differentiation.” From the view of data mining, ZHENG differentiation is modeled as a classification problem. In this paper, ML-kNN—a multilabel learning model—is used as the classification model for hypertension. Feature-level information fusion is also used for further utilization of all information. Experiment results show that ML-kNN can model the hypertension's ZHENG differentiation well. Information fusion helps improve models' performance

Inactivation of the fliY gene encoding a flagellar motor switch protein attenuates mobility and virulence of Leptospira interrogans strain Lai

<p>Abstract</p> <p>Background</p> <p>Pathogenic <it>Leptospira </it>species cause leptospirosis, a zoonotic disease of global importance. The spirochete displays active rotative mobility which may contribute to invasion and diffusion of the pathogen in hosts. FliY is a flagellar motor switch protein that controls flagellar motor direction in other microbes, but its role in <it>Leptospira</it>, and paricularly in pathogenicity remains unknown.</p> <p>Results</p> <p>A suicide plasmid for the <it>fliY </it>gene of <it>Leptospira interrogans </it>serogroup Icterohaemorrhagiae serovar Lai strain Lai that was disrupted by inserting the ampicillin resistance gene (<it>bla</it>) was constructed, and the inactivation of <it>fliY </it>gene in a mutant (<it>fliY</it>^-) was confirmed by PCR and Western Blot analysis. The inactivation resulted in the mRNA absence of <it>fliP </it>and <it>fliQ </it>genes which are located downstream of the <it>fliY </it>gene in the same operon. The mutant displayed visibly weakened rotative motion in liquid medium and its migration on semisolid medium was also markedly attenuated compared to the wild-type strain. Compared to the wild-type strain, the mutant showed much lower levels of adhesion to murine macrophages and apoptosis-inducing ability, and its lethality to guinea pigs was also significantly decreased.</p> <p>Conclusion</p> <p>Inactivation of <it>fliY</it>, by the method used in this paper, clearly had polar effects on downstream genes. The phentotypes observed, including lower pathogenicity, could be a consequence of <it>fliY </it>inactivation, but also a consequence of the polar effects.</p

Association between mesothelin expression and survival outcomes in patients with triple-negative breast cancer: a protocol for a systematic review

PRISMA flow diagram [14]. (DOCX 98 kb

EXTRACTION AND ISOLATION OF ALKALOIDS OF SOPHORA ALOPECUROIDES AND THEIR ANTI-TUMOR EFFECTS IN H22 TUMOR-BEARING MICE

Background: Alkaloids of Sophora alopecuroides have good biological activity, and are widely used in clinical settings, which not only have pharmacological activities of anti-cancer, cancer suppression, as well as the inhibition, and killing of various microorganisms; but also possess extensive pharmacological effects on immune system, nervous system and cardiovascular system. The objective of this paper was to extract and isolate total alkaloids of Sophora alopecuroides (TASA), and to study their anti-tumor effects in H22 tumor-bearing mice. Materials and Methods: TASA were extracted and isolated using thin-layer chromatography, and column chromatography; and the isolated compounds were analyzed using nuclear magnetic resonance. The inhibitory effects of TASA on tumor in H22-bearing mice were determined by MTT assay. Results: Three compounds were isolated from Sophora alopecuroides L., which were matrine, oxymatrine and sophoridine, respectively. Meanwhile, mouse H22 sarcoma model was established and different doses of TASA apparently inhibited solid H22-tumor in mice; it inhibited the thymus, and spleen to some extent; the degree of inhibition was more obvious for the spleen. Conclusion: TASA has an anti-tumor effect in H22 tumor-bearing mice

Effects of Methotrexate on Plasma Cytokines and Cardiac Remodeling and Function in Postmyocarditis Rats

Excessive immune activation and inflammatory mediators may play a critical role in the pathogenesis of chronic heart failure. Methotrexate is a commonly used anti-inflammatory and immunosuppressive drug. In this study, we used a rat model of cardiac myosin-induced experimental autoimmune myocarditis to investigate the effects of low-dose methotrexate (0.1 mg/kg/d for 30 d) on the plasma level of cytokines and cardiac remodeling and function. Our study showed that levels of tumor necrosis factor-(TNF-)alpha and interleukin-6 (IL-6) are significantly increased in postmyocarditis rats, compared with the control rats. Methotrexate treatment reduced the plasma levels of TNF-alpha and IL-6 and increased IL-10 level, compared to saline treatment. In addition, postmyocarditis rats showed significant cardiac fibrosis characterized by increased myocardial collagen volume fraction, perivascular collagen area, and the ratio of collagen type I to type III, compared with the control rats. However, MTX treatment not only markedly attenuated cardiac fibrosis, diminished the left ventricular end-diastolic dimension, but also increased the left ventricular ejection fraction and fractional shortening. Collectively, these results suggest that low-dose methotrexate has ability to regulate inflammatory responses and improves cardiac function and hence contributes to prevent the development of postmyocarditis dilated cardiomyopathy