Integrating Strategies of Herbal Metabolomics, Network Pharmacology, and Experiment Validation to Investigate Frankincense Processing Effects

In-depth research on processing can promote the globalization of processed herbs. The purpose of this study is to propose an improved strategy for processing effect investigation. Frankincense and processed frankincense were used as research subjects. First, high-speed countercurrent chromatography (HSCCC) and preparation high-performance liquid chromatography (PHPLC) techniques were used for major compounds isolation and minor compounds concentration. Processed frankincense was subjected to two stepwise solvent systems, namely, n-hexane:ethanol:water (6:5:1) and n-hexane:methyl-acetate:acetonitrile:water (4:4:3:4), to yield 12 fractions, and 18 compounds were further separated. Second, a comprehensive metabolomic analysis conducted by ultrahigh-performance liquid-chromatography/electrospray-ionization mass spectrometry (UHPLC-Qtof-MS) coupled with multivariate statistics was performed to fully characterize the chemical components and discover the potential biomarkers between frankincense and processed frankincense. In total, 81 metabolites, including the 18 separated compounds, were selected as potential biomarkers between frankincense and processed frankincense among 153 detected compounds for their VIP values of greater than one. The tirucallane-type compounds and components with 9,11-dehydro structures clearly occurred at high levels in the processed frankincense, while lupine-type compounds and those with 11-keto structures were significantly higher in frankincense. Then, a network pharmacology model was constructed to decipher the potential mechanisms of processing. Intestinal absorption properties prediction indicated the possibility of processing-related absorption enhancement. A systematic analysis of the constructed networks showed that the C-T network was constructed with 18 potential biomarkers and 69 targets. TNF and IL-1β were among the top-ranked and were linked by 8 and 7 pathways, which were mainly involved in inflammation. The arachidonic acid metabolism pathway exhibited the highest number of target connections. Finally, the prediction was validated experimentally by an intestinal permeability and efficacy assay. The experiments provided convincing evidence that processed frankincense harbored stronger inhibition effects toward TNF-α-, IL-1β- and arachidonic acid-induced platelet aggregation. The processing procedure leads to changes of the chemical metabolites, which triggers the enhancement of absorption and cure efficiency. The global change of the metabolites, absorption and pharmacological effects of processing were depicted in a systematic manner

Treatment of Rheumatoid Arthritis Using Combination of Methotrexate and Tripterygium Glycosides Tablets—A Quantitative Plasma Pharmacochemical and Pseudotargeted Metabolomic Approach

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by chronic destructive synovitis and is associated with progressive disability, systemic difficulties, premature death, and socioeconomic costs. Early intervention with disease-modifying antirheumatic drugs (DMARDs) like methotrexate (MTX) and its combination regimen would provide obvious benefits to patients, healthcare systems and society. MTX and tripterygium glycosides tablets (TGTS) are most frequently prescribed medicines for RA, and the combination of them occurs frequently in anti-RA prescriptions. While the underlying combination mechanisms and the affected variation of drug blood level remain unclear. According to the American College of Rheumatology criteria for improvement, clinical evaluation following three treatment groups (i.e., MTX and TGTS mono- and combined groups) were carried out at baseline and at the end of 12 weeks in a randomized controlled clinical trial. To monitor the affected variation of drug blood level and perturbation of metabolites caused by MTX plus TGTS combined to treat active RA, the collected plasma samples were analyzed using RRLC-QqQ-MS and UHPLC-QE Orbitrap HRMS instruments. As a result, 39 metabolites including 7 MTX-related metabolites, 13 TGTS-related migratory ingredients and 19 characteristic endogenous metabolites, were quantitatively determined in plasma samples of RA patients after oral administration. The potential mechanism of MTX and TGTS combination were preliminarily elucidated on the aspect of clinical biochemical test indicators integrated with quantitative plasma pharmacochemistry and the pseudotargeted metabolomics

Simultaneous Determination of Seven Components in Rat Plasma by the UPLC-MS/MS Method and Application of Pharmacokinetic Studies to SimiaoYong’an Decoction

SimiaoYong’an Decoction (SYD) is a classical traditional Chinese prescription that is used for the treatment of gangrene, heat-clearing, detoxification and pain alleviation. We developed a sensitive ultra-performance liquid chromatography-tandem mass spectrum (UPLC-MS/MS) method for the simultaneous determination of seven major active ingredients of SYD extract (i.e., harpagide, chlorogenic acid, sweroside, loganin, liquiritin, angoroside C and harpagoside) in rat plasma. The preliminary steps in the plasma analysis were the addition of an internal standard such as linarin, followed by protein precipitation with methanol. Separation of the active ingredients was performed on an ACQUITY UPLC® BEH C18 column (100 mm × 2.1 mm, 1.7 μm) at a flow rate of 0.2 mL/min with methanol/water 0.1% formic acid aqueous (V/V) as the mobile phase. Detection was performed on a triple quadrupole tandem MS (QqQ-MS) via negative ion electrospray ionization in multiple reactions monitoring (MRM) mode. All calibration curves showed good linearity (r > 0.99) over the concentration range with a low limit of quantification between 0.029 and 5.813 ng/mL. Precision was evaluated by intra-day and inter-day assays, and the percentages of the RSD were all within 8.1%. The extraction efficiency and matrix effect were 80.6–113.6% and 82.9–99.5%, respectively. The validated method was successfully applied to a pharmacokinetic study in rats after oral administration of SYD extract and the corresponding single and combined traditional Chinese medicines (TCMs). The pharmacokinetic properties of the seven ingredients showed dynamic changes due to counteraction among the different coexisting components. The established approach has proven useful in the study of the active constituents in a traditional Chinese prescription

Fusing multi-scale information in convolution network for MR image super-resolution reconstruction

Abstract Background Magnetic resonance (MR) images are usually limited by low spatial resolution, which leads to errors in post-processing procedures. Recently, learning-based super-resolution methods, such as sparse coding and super-resolution convolution neural network, have achieved promising reconstruction results in scene images. However, these methods remain insufficient for recovering detailed information from low-resolution MR images due to the limited size of training dataset. Methods To investigate the different edge responses using different convolution kernel sizes, this study employs a multi-scale fusion convolution network (MFCN) to perform super-resolution for MRI images. Unlike traditional convolution networks that simply stack several convolution layers, the proposed network is stacked by multi-scale fusion units (MFUs). Each MFU consists of a main path and some sub-paths and finally fuses all paths within the fusion layer. Results We discussed our experimental network parameters setting using simulated data to achieve trade-offs between the reconstruction performance and computational efficiency. We also conducted super-resolution reconstruction experiments using real datasets of MR brain images and demonstrated that the proposed MFCN has achieved a remarkable improvement in recovering detailed information from MR images and outperforms state-of-the-art methods. Conclusions We have proposed a multi-scale fusion convolution network based on MFUs which extracts different scales features to restore the detail information. The structure of the MFU is helpful for extracting multi-scale information and making full-use of prior knowledge from a few training samples to enhance the spatial resolution

The complete chloroplast genome and phylogenetic position of Thamnocalamus unispiculatus (Poaceae: Bambusoideae: Arundinarieae)

Thamnocalamus unispiculatus T.P.Yi & J.Y.Shi 2007 is an important bamboo species with significant ecological and economic value. This study presents the complete chloroplast genome sequence of T. unispiculatus. The sequence was 139,726 bp in length and exhibited a typical quadripartite structure, containing four regions: large single copy regions (LSC, 83,283 bp), small single copy regions (SSC, 12,851 bp) and a pair of inverted repeats (IRs, 21,726 bp). A total of 130 genes were annotated, including 86 protein-coding genes, 36 transfer RNA genes, and eight ribosomal RNA genes. Phylogenetic analysis indicated that T. unispiculatus and T. spathiflorus are sister species, supporting the conclusion that Thamnocalamus is a monophyletic group. The chloroplast genome of T. unispiculatus promotes the protection and exploration of biodiversity, phylogenetic relationships, and genetic research in Bambusoideae

Crohn′s disease in a child with Wiskott-Aldrich syndrome: a case report and literature review

Objective: To investigate the clinical features, endoscopic manifestations, and genetic characteristics of a child with Wiskott-Aldrich syndrome(WAS) and Crohn′s disease, so as to provide reference for clinical diagnosis. Methods: The clinical manifestations, biological indicators, endoscopic characters, therapy, and follow-up of a child with Crohn′s disease combined with WAS were analyzed retrospectively. And literature was searched from PubMed, Wanfang Data, and CNKI. Results: A 6-year-old boy had recurrent abdominal pain, hematochezia for one month, and had perianal abscess for about half a month. He also had thrombocytopenia since infancy. Complete blood cell count showed moderate anemia (Hb 70 g/L) and decreased platelets (77×109/L). The boy had elevated erythrocyte sedimentation rate (71 mm/h) and fecal calprotectin (>1 800 μg/g). Colonoscopy showed multiple ulcers in colon and the pathological examination revealed chronic inflammation in mucosa of the terminal ileum and colon, some of which were accompanied by microabscess and crypt abscesses. The child was diagnosed with Crohn's disease. A splicing mutation (c.777+3_777+6 del GAGT) was identified in the exon 8 of WAS gene by next-generation sequencing. Consequently, the child was definitely diagnosed as WAS combined with Crohn′s disease. There were 9 relevant articles, showing that all 16 patients had childhood-onset inflammatory bowel disease (IBD) (1 day to 14.9 years old), and 10 of them were accompanied by thrombocytopenia. Various treatments, including drugs, surgery, and bone marrow transplantation were required. Seven patients were followed up, and three of them died. Conclusions: For children with IBD, particularly those with very early-onset inflammatory bowel disease, the possibility of monogenic diseases should be taken into account. If a male child with IBD have thrombocytopenia since childhood, the WAS gene should be detected

Built-up area detection based on a Bayesian saliency model

Built-up area detection is very important for applications such as urban planning, urban growth detection and land use monitoring. In this paper, we address the problem of built up area detection from the perspective of visual saliency computation. Generally, areas containing buildings attract more attentions than forests, lands and other backgrounds. This paper explores a Bayesian saliency model to automatically detect urban areas. Firstly, prior probability is computed by using fast multi-scale edge distribution. Then the likelihood is obtained by modelling the distributions of colour and orientation. Built up areas are further detected by segmenting the final saliency map using Graph Cut algorithm. Experimental results demonstrate that the proposed method can extract built-up area efficiently and accurately

Triglycerides as Biomarker for Predicting Systemic Lupus Erythematosus Related Kidney Injury of Negative Proteinuria

Fewer biomarkers can be used to predict systemic lupus erythematosus (SLE) related kidney injury. This paper presents an apriori algorithm of association rules to mine the predictive biomarkers for SLE-related kidney injury of negative proteinuria. An apriori algorithm of association rules was employed to identify biomarkers, and logistic regression analysis and spearman correlation analysis were used to evaluate the correlation between triglycerides and SLE-related kidney injury of negative proteinuria. Triglycerides were mined out by the apriori algorithm of association rules. The level of triglycerides was significantly higher, and it was an independent risk factor for SLE-related kidney injury. In the high-triglycerides group, the number of patients with SLE-related kidney injury, SLEDAI-2K, urine P-CAST, the level of blood urea nitrogen, serum creatinine, and proteinuria were increased. Triglycerides level was positively correlated with proteinuria and P-CAST and negatively correlated with albumin and IgG. The area under the ROC curve of triglycerides and triglycerides combined proteinuria was 0.72 and 0.82, respectively. Significantly, 50% of SLE-related kidney injuries of negative proteinuria could be identified by high triglycerides levels. High triglycerides level was found at the time of onset of kidney injury, and it was opposite to glomerular filtration rate. Triglycerides may be a potential marker for predicting SLE-related kidney injury, especially in SLE-related kidney injury of negative proteinuria. Triglycerides combined proteinuria could predict SLE-related kidney injury effectively