An integrated analytical strategy to decipher the metabolic profile of alkaloids in Compound Kushen injection based on UHPLC-ESI-QTOF/MSE.

Compound Kushen injection (CKI) is a kind of sterilised water-soluble traditional Chinese medicine preparation that has been used for the clinical treatment of a variety of cancers (hepatocellular carcinoma, lung cancer, etc.) for 19 years. However, to date, the metabolism-related study on CKI in vivo has not been conducted.An integrated analytical strategy was established to investigate the metabolic profile of alkaloids of CKI in rat plasma, urine, and faeces based on ultra-high performance liquid chromatography-electrospray quadrupole time-of-flight mass spectrometry in MSE mode (UHPLC-ESI-QTOF/MSE).Nineteen prototype alkaloids (including 12 matrine-type alkaloids, 2 cytisine-type alkaloids, 3 lupinine-type alkaloids, and 2 aloperine-type alkaloids) of CKI were identified in vivo. Furthermore, 71 metabolites of alkaloids (including 11 of lupanine-related metabolites, 14 of sophoridine-related metabolites, 14 of lamprolobine-related metabolites, and 32 of baptifoline-related metabolites) were tentatively characterised. Metabolic pathways involved in the metabolism of phase I (include oxidation, reduction, hydrolysis, and desaturation), phase II (mainly include glucuronidation, acetylcysteine or cysteine conjugation, methylation, acetylation, and sulphation), and associated combination reactions.The integrated analytical strategy was successfully used to characterise the prototype alkaloids and their metabolites of CKI in vivo, and the results laying a foundation for further study its pharmacodynamic substances.

Integrated analysis of metabolomic and transcriptomic profiling reveals the effect of Buyang Huanwu decoction on Parkinson's disease in mice.

BACKGROUND: Parkinson's disease (PD) is a common, complex, and chronic neurodegenerative disorder involved in multi-system. At present, medicine for PD has many limitations. Buyang Huanwu decoction (BHD), a famous traditional Chinese medicinal (TCM) formulae, is used in the treatment of PD clinically in China. However, the therapeutic mechanism is still unknown. PURPOSE: We aimed to explore the pharmacological mechanism of BHD alleviating PD through an integrated liver metabolome and brain transcriptome analysis. METHODS: The mice with PD were induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Behavioral tests and immunohistochemistry were used to evaluate the neuroprotective effects of BHD. The non-targeted metabolomics analysis was conducted to profile differentially accumulated metabolites (DAMs) in the liver using a UHPLC-Q-Exactive MS/MS method. The differentially expressed genes (DEGs) in the brain were investigated by transcriptomic analysis on an Illumina sequencing platform. The correlations of DAMs and DEGs were investigated using an integrated metabolomic and transcriptomic approach. RESULTS: The results of behavioral tests and immunohistochemistry proved the alleviated effects of BHD on PD symptoms. A total of 14 and 36 DAMs were detected in the groups treated with low- (L group) and high-dose (H group) BHD respectively under the positive ion mode. Compared with the PD model group (M group), three enriched pathways including metabolic pathways, ABC transporters, and biosynthesis of amino acids were common in the L and H group. Transcriptomic analysis proved that BHD could regulate the expression of numerous genes, some of which were targeted by Ben-Ldopa such as Creb5, Gm45623, Ccer2, Cd180, Fosl2, Crip3, and Noxred1. Based on the integrated metabolomic and transcriptomic analysis, 7 metabolite-gene pairs were found in four comparisons, including C vs M, M vs P, M vs L, and M vs H, and 6 enriched pathways containing purine metabolism, glycine/serine/threonine metabolism, phenylalanine metabolism, carbon fixation in photosynthetic organisms, thiamine metabolism, and ABC transporters were overlapped. CONCLUSIONS: Though the underlying pharmacological mechanism of BHD is still lacking, we provided evidence that BHD could improve dopaminergic neurons in MPTP-induced PD mice by regulating liver metabolism and brain transcriptome. The correlation between the liver and the brain was preliminarily revealed in this study.

Primary Malignant Melanoma of the Cervix: An Integrated Analysis of Case Reports and Series.

Melanoma, also known as malignant melanoma, is a type of malignant tumour that originates from melanocytes in the basal layer of the epidermis. Primary malignant melanomas of the female genital tract are rare. Similarly, primary malignant melanoma of cervix, which originates from cervical melanocytes, is an extremely rare disease and the second most common type of female melanoma in women aged between 15 to 44 years worldwide. To date, primary malignant melanoma of the cervix is characterized by poor patient prognosis and little consensus exists regarding the best treatment therapy. The situation is worsened by lack of clinical studies with large samples. Notably, surgery remains the preferred treatment option for patients with primary malignant melanomas of the cervix. Current treatments are based on Federation International of Gynecology and Obstetrics(2018) staging with reference to National Comprehensive Cancer Network guidelines. This study is in order to find a more suitable treatment modality for primary malignant melanoma of cervix. Therefore, we first conducted an integrated analysis of case reports and series to assess the impact of various factors on the prognosis of such patients. In summary, this is the first pooled analysis including 149 cases of primary cervical melanoma. We found that patients who underwent radical hysterectomy-based surgery, those with non-metastatic lymph nodes and those who underwent lymphadenectomy had significantly higher survival rates. In patients who had RH-based surgery, survival rates at the 24m time point of those who did not add other treatments was higher than those who did, but for those who had total hysterectomy-based surgery, the addition of other treatments to prolong median survival may be considered. In the overall analysis, age and lymphadenectomy were associated with increased and reduced risk of death in these patients, respectively. Although there is no statistical difference, stage III&IV, TAH, lymphatic metastases increase the risk of death; whereas radical hysterectomy was associated with reduced risk of death. In the subgroup analysis, for patients who have undergone radical hysterectomy-based surgery, lymphadenectomy reduces the risk of death, while lymphatic metastases and complementary other treatments increase the risk of death. For patients who have undergone total hysterectomy-based surgery, complementary treatment reduces the risk of death. In conclusion, via summarizing previous reports, the recommended treatment procedure for PMMC are radical hysterectomy and lymphadenectomy. The addition of other treatment options for patients who undergoing RH-based surgery need further study.

Remodeling and protecting the membrane system to resist phosphorus deficiency in wild soybean (Glycine soja) seedling leaves.

MAIN CONCLUSION: The poor-soil-tolerant wild soybean resist phosphorus deficiency by remodeling membrane lipids to reuse phosphorus. The plants synthesize phenolic acids and flavonoids to remove reactive oxygen species and protect membrane stability. Poor soil largely limits plant yields, and the development and utilization of high-quality wild plant resources is an effective approach to resolving this problem. Two ecotypes of wild soybean were used as experimental materials in this experiment. We integrated metabolomics and transcriptomics to determine whether wild soybean (Glycine soja) could resist phosphorus deficiency by remodeling and protecting its membrane system. Under phosphorus-deficient conditions, the plant height and aboveground fresh and dry weight of poor-soil-tolerant wild soybean seedlings were less inhibited than those in common wild soybean. In poor-soil-tolerant wild soybean seedling leaves, the glycerol-3-phosphate content decreased significantly, while caffeic acid, ferulic acid, shikimic acid, phenylalanine, tyrosine, and tryptophan increased significantly. ß-Glucosidase and chalcone synthase genes and those that encode SQD2, a crucial enzyme in thiolipid biosynthesis, were specifically up-regulated, whereas the glucosyltransferase UGT74B1 gene was down-regulated. The poor-soil-tolerant wild soybean enhanced glycerolipid metabolism to decompose phospholipids and release phosphorus for reuse to improve resistance to phosphorus deficiency. The plants synthesized thiolipids to replace phospholipids and maintain membrane structure integrity and inhibited glucosinolate biosynthesis to promote phenylpropanoid biosynthesis, leading to the production of phenolic acids and flavonoids that removed reactive oxygen species and protected membrane system stability. The experiments evaluated and provided insight into the innovative utilization of wild soybean germplasm resources.

Integrated microRNA and transcriptome profiling reveal key miRNA-mRNA interaction pairs associated with seed development in Tartary buckwheat (Fagopyrum tataricum).

BACKGROUND: Tartary buckwheat seed development is an extremely complex process involving many gene regulatory pathways. MicroRNAs (miRNAs) have been identified as the important negative regulators of gene expression and performed crucial regulatory roles in various plant biological processes. However, whether miRNAs participate in Tartary buckwheat seed development remains unexplored. RESULTS: In this study, we first identified 26 miRNA biosynthesis genes in the Tartary buckwheat genome and described their phylogeny and expression profiling. Then we performed small RNA (sRNA) sequencing for Tartary buckwheat seeds at three developmental stages to identify the miRNAs associated with seed development. In total, 230 miRNAs, including 101 conserved and 129 novel miRNAs, were first identified in Tartary buckwheat, and 3268 target genes were successfully predicted. Among these miRNAs, 76 exhibited differential expression during seed development, and 1534 target genes which correspond to 74 differentially expressed miRNAs (DEMs) were identified. Based on integrated analysis of DEMs and their targets expression, 65 miRNA-mRNA interaction pairs (25 DEMs corresponding to 65 target genes) were identified that exhibited significantly opposite expression during Tartary buckwheat seed development, and 6 of the miRNA-mRNA pairs were further verified by quantitative real-time polymerase chain reaction (qRT-PCR) and ligase-mediated rapid amplification of 5' cDNA ends (5'-RLM-RACE). Functional annotation of the 65 target mRNAs showed that 56 miRNA-mRNA interaction pairs major involved in cell differentiation and proliferation, cell elongation, hormones response, organogenesis, embryo and endosperm development, seed size, mineral elements transport, and flavonoid biosynthesis, which indicated that they are the key miRNA-mRNA pairs for Tartary buckwheat seed development. CONCLUSIONS: Our findings provided insights for the first time into miRNA-mediated regulatory pathways in Tartary buckwheat seed development and suggested that miRNAs play important role in Tartary buckwheat seed development. These findings will be help to study the roles and regulatory mechanism of miRNAs in Tartary buckwheat seed development.

Integrated Bioinformatics Analysis for the Screening of Associated Pathways and Therapeutic Drugs in Coronavirus Disease 2019.

BACKGROUND: COVID-19 caused by a novel coronavirus, a severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), has recently broken out worldwide. Up to now, the development of vaccine is still in the stage of clinical research, and there is no clinically approved specific antiviral drug for human coronavirus infection. The purpose of this study is to investigate the key molecules involved in response during SARS-CoV-2 infection and provide references for the treatment of SARS-CoV-2. METHODS: We conducted in-depth and comprehensive bioinformatics analysis of human proteins identified with SARS-CoV-2, including functional enrichment analysis, protein interaction network analysis, screening of hub genes, and evaluation of their potential as therapeutic targets. In addition, we used the gene-drug database to search for inhibitors of related biological targets. RESULTS: Several significant pathways, such as PKA, centrosome and transcriptional regulation, may greatly contribute to the development and progression of COVID-2019 disease. Taken together 15 drugs and 18 herb ingredients were screened as potential drugs for viral treatment. Specially, the trans-resveratrol can significantly reduce the expression of N protein of MERS-CoV and inhibit MERS-CoV. In addition, trans-resveratrol, Epigallocatechin-3-gallate (EGCG) and BX795 all show good anti multiple virus effects. CONCLUSION: Some drugs selected through our methods have been proven to have antiviral effects in previous studies. We aim to use global bioinformatics analysis to provide insights to assist in the design of new drugs and provide new choices for clinical treatment.

Integrated analysis of DNA methylation and gene expression profiles identified S100A9 as a potential biomarker in ulcerative colitis.

Ulcerative colitis (UC) is a prevalent relapsing-remitting inflammatory bowel disease whose pathogenetic mechanisms remain elusive. In the present study, colonic biopsies samples from three UC patients treated in the Traditional Chinese Medicine Hospital and three healthy controls were obtained. The genome-wide mRNA and lncRNA expression of the samples were profiled through Agilent gene expression microarray. Moreover, the genome-wide DNA methylation dataset of normal and UC colon tissues was also downloaded from GEO for a collaborative analysis. Differential expression of lncRNA (DELs) and mRNAs (DEMs) in UC samples compared with healthy samples were identified by using limma Bioconductor package. Differentially methylated promoters (DMPs) in UC samples compared with controls were obtained through comparing the average methylation level of CpGs located at promoters by using t-test. Functional enrichment analysis was performed by the DAVID. STRING database was applied to the construction of gene functional interaction network. As a result, 2090 DEMs and 1242 DELs were screened out in UC samples that were closely associated with processes related to complement and coagulation cascades, osteoclast differentiation vaccinia, and hemorrhagic diseases. A total of 90 DEMs and 72 DELs were retained for the construction of functional network for the promoters of their corresponding genes were identified as DMPs. S100A9, HECW2, SOD3 and HIX0114733 showed high interaction degrees in the functional network, and expression of S100A9 was confirmed to be significantly elevated in colon tissues of UC patients compared with that of controls by qRT-PCR that was consistent with gene microarray analysis. These indicate that S100A9 could potentially be used as predictive biomarkers in UC.

Metabolomics of Milk Reflects a Negative Energy Balance in Cows.

Dairy cows can experience a negative energy balance (NEB) in early lactation when feed intake is too low to meet the energy requirements for body maintenance and milk production. Metabolic changes occur in mammary gland cells of animals experiencing a negative energy balance. We studied these metabolic changes in milk samples from dairy cows in relation to energy balance status using liquid chromatography-mass spectrometry (QQQ-LC-MS) and nuclear magnetic resonance (1H NMR). NMR and LC-MS techniques are complementary techniques that enabled a comprehensive overview of milk metabolites in our study. Energy balance and milk samples were obtained from 87 dairy cows. A total of 55 milk metabolites were reliably detected, of which 15 metabolites were positively correlated to energy balance and 20 were negatively correlated to energy balance. Cows in NEB produced more milk with increased milk fat yield and higher concentrations of citrate, cis-aconitate, creatinine, glycine, phosphocreatine, galactose-1-phosphate, glucose-1-phosphate, UDP-N-acetyl-galactosamine, UDP-N-acetyl-glucosamine, and phosphocholine but lower concentrations of choline, ethanolamine, fucose, N-acetyl-neuraminic acid, N-acetyl-glucosamine, and N-acetyl-galactosamine. During NEB, we observed an increased leakage of cellular content, increased synthesis of nucleic acids and cell membrane phospholipids, an increase in one-carbon metabolic processes, and an increase in lipid-triglyceride anabolism. Overall, both apoptosis combined with cellular renewal is paramount in the mammary gland in cows in NEB.

Integrated analysis and network pharmacology approaches to explore key genes of Xingnaojing for treatment of Alzheimer's disease.

BACKGROUND: Alzheimer's disease (AD), as a neurodegenerative condition, is one of the leading causes of dementia. Our study aims to explore the key genes of Xingnaojing (XNJ) for treatment of AD by integrated microarray analysis and network pharmacology. METHODS: The differentially expressed genes (DEGs) were identified in AD compared with normal control. According to these DEGs, we performed the functional annotation, protein-protein interaction (PPI) network construction. The network pharmacology was used to explore the potential targets of XNJ in the treatment of AD. The expression level of selected candidate genes was validated by quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: A total of 1,424 DEGs (620 genes were upregulated and 804 genes were downregulated) between AD and normal control were obtained. The functional annotation results displayed that neuroactive ligand-receptor interaction, regulation of actin cytoskeleton, Estrogen signaling pathway and notch signaling pathway were significantly enriched pathways in AD. Comparing the target genes of four active ingredients, a total of 16 shared genes were found. Among which, HTR2A and ADRA2A were also enriched in pathway of neuroactive ligand-receptor interaction. The expression of 4 DEGs (SORCS3, HTR2A, NEFL, and TAC1) was validated by qRT-PCR. Except for TAC1, the other 3 DEGs in AD were consistent with our integrated analysis. CONCLUSIONS: The results of this study may provide novel insights into the molecular mechanisms of AD and indicate potential therapeutic targets for AD.

Integrated transcriptome and miRNA analysis uncovers molecular regulators of aerial stem-to-rhizome transition in the medical herb Gynostemma pentaphyllum.

BACKGROUND: Gynostemma pentaphyllum is an important perennial medicinal herb belonging to the family Cucurbitaceae. Aerial stem-to-rhizome transition before entering the winter is an adaptive regenerative strategy in G. pentaphyllum that enables it to survive during winter. However, the molecular regulation of aerial stem-to-rhizome transition is unknown in plants. Here, integrated transcriptome and miRNA analysis was conducted to investigate the regulatory network of stem-to-rhizome transition. RESULTS: Nine transcriptome libraries prepared from stem/rhizome samples collected at three stages of developmental stem-to-rhizome transition were sequenced and a total of 5428 differentially expressed genes (DEGs) were identified. DEGs associated with gravitropism, cell wall biosynthesis, photoperiod, hormone signaling, and carbohydrate metabolism were found to regulate stem-to-rhizome transition. Nine small RNA libraries were parallelly sequenced, and seven significantly differentially expressed miRNAs (DEMs) were identified, including four known and three novel miRNAs. The seven DEMs targeted 123 mRNAs, and six pairs of miRNA-target showed significantly opposite expression trends. The GpmiR166b-GpECH2 module involved in stem-to-rhizome transition probably promotes cell expansion by IBA-to-IAA conversion, and the GpmiR166e-GpSGT-like module probably protects IAA from degradation, thereby promoting rhizome formation. GpmiR156a was found to be involved in stem-to-rhizome transition by inhibiting the expression of GpSPL13A/GpSPL6, which are believed to negatively regulate vegetative phase transition. GpmiR156a and a novel miRNA Co.47071 co-repressed the expression of growth inhibitor GpRAV-like during stem-to-rhizome transition. These miRNAs and their targets were first reported to be involved in the formation of rhizomes. In this study, the expression patterns of DEGs, DEMs and their targets were further validated by quantitative real-time PCR, supporting the reliability of sequencing data. CONCLUSIONS: Our study revealed a comprehensive molecular network regulating the transition of aerial stem to rhizome in G. pentaphyllum. These results broaden our understanding of developmental phase transitions in plants.

Liver-specific metabolomics characterizes the hepatotoxicity of Dioscorea bulbifera rhizome in rats by integration of GC-MS and 1H-NMR.

ETHNOPHARMACOLOGICAL RELEVANCE: Dioscorea bulbifera rhizome (DBR), one type of herbal medicine, is extensively used in both Indian and Chinese system of traditional medicine. It has been effective in treating various diseases, such as sore throat, struma, and tumors. However, more and more clinical investigations have suggested that DBR can cause liver injury. AIM OF THE STUDY: In the present study, we aimed to characterize the corresponding molecular changes of liver dysfunction and reveal overall metabolic and physiological mechanisms of the subchronic toxic effect of DBR. MATERIALS AND METHODS: A liver-specific metabolomics approach integrating GC-MS and 1H-NMR was developed to assess the hepatotoxicity in rats after DBR exposure for 12 weeks. Multivariate statistical analysis and pattern recognition were employed to examine different metabolic profiles of liver in DBR-challenged rats. RESULTS: A total of 61 metabolites were screened as significantly altered metabolites, which were distributed in 43 metabolic pathways. The correlation network analysis indicated that the hub metabolites of hepatotoxicity could be mainly linked to amino acid, lipid, purine, pyrimidine, bile acid, gut microflora, and energy metabolisms. Notably, purine, pyrimidine, and gut microflora metabolisms might be novel pathways participating in metabolic abnormalities in rats with DBR-triggered hepatic damage. CONCLUSIONS: Our results primarily showed that the liver-specific metabolic information provided by the different analytical platforms was essential for identifying more biomarkers and metabolic pathways, and our findings provided novel insights into understand the mechanistic complexity of herb-induced liver injury.

Integration of microRNA-mRNA profiles and pathway analysis of plant isoquinoline alkaloid berberine in SGC-7901 gastric cancers cells.

PURPOSE: Berberine (BBR) is a traditional Chinese medicine normally used for gastroenteritis, and recent research found that it could fight against tumors. In this study, we focused on integrating miRNA sequencing and RNA sequencing of SGC-7901 gastric cancer cells treated by BBR to elucidate their underlying mechanisms. MATERIALS AND METHODS: WST-1 assay and flow cytometry were used to check the effects of BBR on SGC-7901. miRNA sequencing and RNA sequencing were used to establish the miRNA and mRNA profiles of BBR-treated SGC-7901. RESULTS: The results showed that BBR could inhibit the proliferation of SGC-7901 cells and induce G1 arrest in cell cycle phase and apoptosis. A total of 1,960 upregulated genes and 4,837 downregulated genes were identified in the RNA sequencing and 347 upregulated and 93 downregulated miRNAs in the miRNA sequencing. A total of 78 novel miRNAs were also found. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis showed that the genes were related to pathways in cancer and metabolism. We also analyzed the miRNA-mRNA network of genes grouped into cell cycle, apoptosis, inflammation, metabolism, cell junction, acetylization process, TGF-ß pathway, and Wnt signaling pathway. CONCLUSION: BBR could inhibit the proliferation of SGC-7901 cells and induce apoptosis. Integrated analysis of microRNA-mRNA profiles is a promising approach to validate gene expression patterns associated with malignant phenotype and study the mechanisms of anticancer.

[Rapid identification and evaluation of Chinese materia medica quality by near infrared spectroscopy].

In recent years, the research object of traditional Chinese medicine(TCM) analysis has not just been limited to the common analysis technology, but focused on the key relationship between chemical ingredients and traditional functions, including Chinese material medica (CMM) attributes, chemical substance and biological function. Near infrared spectroscopy (NIR) analysis technology, due to its unique advantages, has been developed rapidly in the field of pharmaceutical analysis, especially in the TCM analysis. NIRS can reflect the global chemical information comprehensively, and this holistic approach can be used for the identification and cluster analysis of CMM. On the other hand, inspiring by the concept of TCM quality markers (Q-markers), by means of the activity screening assay of the key components from the CMM, multiple bioactive components quantitation can be achieved by the NIRS combined with chemometrics. Taking the full advantage of the NIR technology, a simple and reliable method for the fast evaluation of the quality of TCMs can be provided. Therefore, the progress and trend of modern TCM quality evaluation by NIR are discussed and prospected in the present review.

Rapid identification and evaluation of Chinese materia medica quality by near infrared spectroscopy / 中国中药杂志

In recent years, the research object of traditional Chinese medicine(TCM) analysis has not just been limited to the common analysis technology, but focused on the key relationship between chemical ingredients and traditional functions, including Chinese material medica (CMM) attributes, chemical substance and biological function. Near infrared spectroscopy (NIR) analysis technology, due to its unique advantages, has been developed rapidly in the field of pharmaceutical analysis, especially in the TCM analysis. NIRS can reflect the global chemical information comprehensively, and this holistic approach can be used for the identification and cluster analysis of CMM. On the other hand, inspiring by the concept of TCM quality markers (Q-markers), by means of the activity screening assay of the key components from the CMM, multiple bioactive components quantitation can be achieved by the NIRS combined with chemometrics. Taking the full advantage of the NIR technology, a simple and reliable method for the fast evaluation of the quality of TCMs can be provided. Therefore, the progress and trend of modern TCM quality evaluation by NIR are discussed and prospected in the present review.

The effects of atomoxetine on emotional control in adults with ADHD: An integrated analysis of multicenter studies.

PURPOSE: To investigate the effects of atomoxetine on emotional control in adults with ADHD. METHODS: We performed an integrated analysis using individual patient data pooled from three Eli Lilly-sponsored studies. An integrated analysis can be viewed as a meta-analysis of individual patient-level data, rather than study-level summary data. RESULTS: Two populations were identified: a large sample of patients with pre-treatment baseline data (the "overall population"; n=2846); and a subset of these patients with placebo-controlled efficacy data from baseline to 10 or 12 weeks after initiating treatment (the "placebo-controlled population"; n=829). At baseline, in the overall population, ∼50% of ADHD patients had BRIEF-AS (Behavior Rating Inventory of Executive Function-Adult Version Self-Report) Emotional control subscores between 21 and 30, compared with ∼10% of normative subjects in the BRIEF-A manual. At endpoint, in the placebo-controlled population, atomoxetine led to a small (effect size 0.19) but significant (P=0.013) treatment effect for emotional control. The effect size was 0.32 in patients with BRIEF-AS Emotional control scores>20 at baseline. Improvements in emotional control correlated with improvements in the core ADHD symptoms and quality-of-life. DISCUSSION: As deficient emotional control is associated with impaired social, educational and occupational functioning over and above that explained by core ADHD symptoms alone, improvements in emotional control may be clinically relevant. CONCLUSION: At baseline, adults with ADHD were more likely to have impaired emotional control than normative subjects. In the adult ADHD patients, atomoxetine treatment was associated with improvements in emotional control, as well as in core ADHD symptoms and quality-of-life.

An integrated analysis for determining the geographical origin of medicinal herbs using ICP-AES/ICP-MS and (1)H NMR analysis.

ICP-MS and (1)H NMR are commonly used to determine the geographical origin of food and crops. In this study, data from multielemental analysis performed by ICP-AES/ICP-MS and metabolomic data obtained from (1)H NMR were integrated to improve the reliability of determining the geographical origin of medicinal herbs. Astragalus membranaceus and Paeonia albiflora with different origins in Korea and China were analysed by (1)H NMR and ICP-AES/ICP-MS, and an integrated multivariate analysis was performed to characterise the differences between their origins. Four classification methods were applied: linear discriminant analysis (LDA), k-nearest neighbour classification (KNN), support vector machines (SVM), and partial least squares-discriminant analysis (PLS-DA). Results were compared using leave-one-out cross-validation and external validation. The integration of multielemental and metabolomic data was more suitable for determining geographical origin than the use of each individual data set alone. The integration of the two analytical techniques allowed diverse environmental factors such as climate and geology, to be considered. Our study suggests that an appropriate integration of different types of analytical data is useful for determining the geographical origin of food and crops with a high degree of reliability.