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Additional file 3. Transmembrane domain prediction of the NSLC protein.

Additional file 1. Analysis results of the amino acid sequences of EnNA4 (A), EtSAG1 (B), EaLDH (C), and EmCDPK (D) using DNAStar Protean software. The amino acids in the red box were selected to construct the fusion protein.

Additional file 4. Primers used for PCR amplification.

Polygonum capitatum has unique curative effects on the urinary system. In fact, many Polygonum capitatum-based preparations are currently used in the clinic. In China, the combination of levofloxacin (LVFX) with a Chinese herbal preparation derived from Polygonum capitatum has been used for the clinical treatment of urinary system diseases, which can improve the curative effects and reduce the side effects of LVFX. However, the herb-drug interaction (HDI) between these drugs has not been reported and the effect of Polygonum capitatum on the in vivo process of LVFX is unclear. In this article, a sensitive ultraperformance liquid chromatography-tandem mass spectroscopy (UPLC-MS/MS) method was developed to evaluate the effects of the combined application of LVFX and the Polygonum capitatum extract on tissue distribution and excretion. Thereafter, the method was validated for selectivity, accuracy, precision, linearity, lower limit of quantification (LLOQ), dilution integrity, recovery, and matrix effect. Based on tissue distribution, LVFX could diffuse into all of the tested tissues, with significant differences in the content of each tissue between the coadministration group and single administration group. At 48 h after the combination was orally administered, the urinary cumulative excretion of LVFX decreased from 20.69% to 11.84% while its fecal cumulative excretion decreased from 26.08% to 13.28%. Our results suggest that a drug interaction exists between the two drugs in the process of distribution and excretion. This study provides important experimental evidence for further studies on the clinical efficacy and mechanism of the Polygonum capitatum extract and LVFX.

Laportea bulbifera (Siebold & Zucc.) Wedd., Urticaceae, is a medicinal herb customarily used by the Miao people in China, for the treatment of rheumatism, traumatic injury, and other symptoms. The aim of this study was to develop and validate a sensitive and reliable high-performance liquid chromatography-tandem mass spectrometry method for the simultaneous quantitation of five constituents, including neochlorogenic acid, chlorogenic acid, cryptochlorogenic acid, rutin, and kaempferol-3-O-rutinoside, of L. bulbifera extract in biological samples, and to apply the method to a pharmacokinetic study. The validated method was successfully applied to a pharmacokinetic study in rats with oral administration of L. bulbifera extract at a single dose of 8.3 g kg−1. The five constituents were detected and their pharmacokinetic parameters were calculated. The established method was rapid and sensitive and could be used for the pharmacokinetic study of L. bulbifera extract.

The study aimed to compare the pharmacokinetic properties of quercitrin, astragalin, afzelin and taxifolin, four major bioactive components of Polygonum orientale inflorescence extracts, between sham-operated and myocardial ischemia-reperfusion injury (MIRI) rats.Rats were divided into two groups: MIRI model and sham-operated. The blood samples were collected according to the time schedule. The levels of quercitrin, astragalin, afzelin and taxifolin in the plasma at designated time points were determined using an HPLC-MS/MS method. Various pharmacokinetic parameters were estimated from the plasma concentration versus time data using non-compartmental methods. After the administration of the Chinese herb Polygonum orientale inflorescence extracts, the Cmax, AUC, as well as MRT, increased, while CL decreased, in MIRI model compared to the sham-operated animals.These results suggest that the pathological damage of ischemia-reperfusion had a significant impact on the pharmacological effects of Polygonum orientale inflorescence extracts on ischemic heart disease.The method had been successfully applied to evaluate the pharmacokinetics of quercitrin, astragalin, afzelin and taxifolin in rat plasma after the oral administration of Chinese herb Polygonum orientale inflorescence extracts in rats.

Background Aidi Injection (ADI), a Chinese herbal preparation with anti-cancer activity, is used for the treatment of hepatocellular carcinoma (HCC). Several clinical studies have shown that co-administration of ADI with doxorubicin (DOX) is associated with reduced toxicity of chemotherapy, enhanced clinical efficacy and improved quality of life for patients. However, limited information is available about the herb-drug interactions between ADI and DOX. The study aimed to investigate the pharmacokinetic mechanism of herb-drug interactions between ADI and DOX in a rat model of HCC. Methods Experimental HCC was induced in rats by oral administration of diethylnitrosamine. The HCC rats were pretreated with ADI (10 mL/kg, intraperitoneal injection) for 14 consecutive days prior to administration of DOX (7 mg/kg, intravenous injection) to investigate pharmacokinetic interactions. Plasma concentrations of DOX and its major metabolite, doxorubicinol (DOXol), were determined using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Results Preadministration of ADI significantly altered the pharmacokinetics of DOX in HCC rats, leading to increased plasma concentrations of both DOX and DOXol. The area under the plasma drug concentration-time curve (AUCs) of DOX and DOXol in rats pretreated with ADI were 3.79-fold and 2.92-fold higher, respectively, than those in control rats that did not receive ADI. Conclusions Increased levels of DOX and DOXol were found in the plasma of HCC rats pretreated with ADI.

Background Patient SE translation (SET) belongs to histone chaperone nucleosome assembly protein family and has been confirmed that it is associated with carcinogenesis, tumor progression and patient outcome. In this study, we aim at assessing the prognostic value of SET mRNA, the function and pathway of SET and its related genes in breast cancer. Methods The clinicopathological and prognostic significance of SET was assessed by the molecular taxonomy of breast cancer international consortium (METABRIC) database (n=1,904). Additionally, based on the data and network of SET and its related genes from cBioPortal website, their function in the progression of breast cancer was also explored. Results SET mRNA overexpression was a significant predictor of a poor prognosis (P=0.0006). The two signaling pathways associated with SET were the facilitating function of condensin II on mitosis and the accelerated transportation of tumor cell mRNA towards the extranuclear position, and SET acted to suppress condensin II and stabilize mRNA. Conclusions Owing to the regulation of chromosome condensation and stabilization of tumor cell mRNA, overexpression of SET is correlated with aggressive phenotypes and facilitates tumor proliferation and deterioration. SET may act as a valuable prognosis biomarker in breast cancer.

Identifying disease risk genes is a central topic of human genetics. Cost-effective exome and whole genome sequencing enabled large-scale discovery of genetic variations. However, the statistical power of finding new risk genes through rare genetic variation is fundamentally limited by sample sizes. As a result, we have an incomplete understanding of genetic architecture and molecular etiology of most of human conditions and diseases. In this thesis, I developed new computational methods that integrate functional genomics data sets, such as epigenomic profiles and single-cell transcriptomics, to improve power for identifying genetic risks and gain more insights on etiology of developmental disorders. The overall hypothesis that disease risk genes contributing to developmental disorders are bottleneck genes under normal development and subject to precise transcriptional regulations to maintain spatiotemporal specific expression during development. In this thesis I describe two major research projects. The first project, Episcore, predicts haploinsufficient genes based on a large integrated epigenomic profiles from multiple tissues and cell lines by supervised machine learning methods. The second one, A-risk, predicts plausibility of being risk genes of autism spectrum disorder based on single-cell RNA-seq data collected in human fetal midbrain and prefrontal cortex. Both methods were shown to be able to improve gene discovery in analysis of de novo mutations in developmental disorders. Overall, my thesis represents an effort to integrate functional genomics data by machine learning to facilitate both discovery and interpretation of genetic studies of human diseases. We believe that such integrative analysis can help us better understand genetic variants and disease etiology.