scholarly journals Metabolite Profile Changes in Different Regions of Rat Brain Affected by Ephedra sinica

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Zhou Liao ◽  
Shanshan Li ◽  
Yun Huang ◽  
Xiaoquan Luo ◽  
Youbao Zhong ◽  
...  

Ephedra sinica Stapf (EP) has a long medication history dating back centuries in the world. There were some reports of adverse effects in the central nervous system (CNS) resulting from administration of a drug containing EP or ephedrine. Compared with alkaloid monomer compounds, the effects of EP on the CNS are usually neglected. It is necessary to explore CNS affection which is helpful to use EP rationally. However, the affection and the changes of substances by EP in the brain are still unknown because the effects of drug on the brain also exhibit different tendency and distribution and usually lead to diversity of metabolite alteration in different regions. In this study, metabolomics based on different brain regions was used to investigate the affection mechanism of EP in the CNS. The metabolites in 6 brain regions from a rat that underwent oral administration with EP for 14 days were determined by UPLC/Q-TOF-MS. Brain histological examinations showed that there were no obvious lesions in EP administration groups. Partial least square-discriminant analysis (PLS-DA) displayed that there were significant separations between control and EP administration groups. 7 CNS biomarkers were found and identified in different regions. 3 metabolic pathways were disturbed by EP, including amino acid metabolism, phospholipid metabolism, and amino sugar metabolism. Furthermore, all biomarkers were significantly changed in the cortex after administration. This study may be helpful to understand the affection mechanism of EP in the CNS and improve cognition of brain regional characteristics.

2020 ◽  
Author(s):  
Xu Huan-Hua ◽  
Zhen-Hong Jiang ◽  
Cong-Shu Huang ◽  
Yu-Ting Sun ◽  
Long-Long Xu ◽  
...  

Abstract Background: OPD and OPD' are the two main active components of Ophiopogon japonicas in Shenmai injection (SMI). Being isomers of each other, they are supposed to have similar pharmacological activities, but the actual situation is complicated. The difference of hemolytic behavior between OPD and OPD' in vivo and in vitro was discovered and reported by our group for the first time. In vitro, only OPD' showed hemolysis reaction, while in vivo, both OPD and OPD' caused hemolysis. The primary cause of hemolysis in vitro has been confirmed to be related to the difference between physical and chemical properties of OPD and OPD', but the mechanism of hemolysis in vivo is still unclear, especially the existing research are still difficult to explain why OPD shows the inconsistent hemolysis behavior in vivo and in vitro. Therefore, the study of hemolysis of OPD and OPD' in vivo is of great practical significance in response to the increase of adverse events of SMI.Methods: Aiming at the hemolysis in vivo, this manuscript adopted untargeted metabolomics and lipidomics technology to preliminarily explore the changes of plasma metabolites and lipids of OPD- and OPD'-treated rats. Metabolomics and lipidomics analyses were performed on ultra-high performance liquid chromatography (UPLC) system tandem with different mass spectrometers (MS) and different columns respectively. Multivariate statistical approaches such as principal component analysis (PCA) and orthogonal partial least square-discriminant analysis (OPLS-DA) were applied to screen the differential metabolites and lipids.Results: Both OPD and OPD' groups experienced hemolysis, Changes in endogenous differential metabolites and differential lipids, enrichment of differential metabolic pathways, and correlation analysis of differential metabolites and lipids all indicated that the causes of hemolysis by OPD and OPD' were closely related to the interference of phospholipid metabolism.Conclusions: This study confirmed that interference of phospholipid metabolism was the main cause of hemolysis of OPD and OPD'. This study provided a comprehensive description of metabolome and lipidomic changes under the condition of hemolysis which caused by OPD and OPD'. It can also provide clues for research on the hemolysis mechanism of traditional Chinese medicine.


2021 ◽  
Vol 12 ◽  
Author(s):  
Gurpreet Singh Jutley ◽  
Kalvin Sahota ◽  
Ilfita Sahbudin ◽  
Andrew Filer ◽  
Thurayya Arayssi ◽  
...  

BackgroundSystemic inflammation in rheumatoid arthritis (RA) is associated with metabolic changes. We used nuclear magnetic resonance (NMR) spectroscopy–based metabolomics to assess the relationship between an objective measure of systemic inflammation [C-reactive protein (CRP)] and both the serum and urinary metabolome in patients with newly presenting RA.MethodsSerum (n=126) and urine (n=83) samples were collected at initial presentation from disease modifying anti-rheumatic drug naïve RA patients for metabolomic profile assessment using 1-dimensional 1H-NMR spectroscopy. Metabolomics data were analysed using partial least square regression (PLS-R) and orthogonal projections to latent structure discriminant analysis (OPLS-DA) with cross validation.ResultsUsing PLS-R analysis, a relationship between the level of inflammation, as assessed by CRP, and the serum (p=0.001) and urinary (p<0.001) metabolome was detectable. Likewise, following categorisation of CRP into tertiles, patients in the lowest CRP tertile and the highest CRP tertile were statistically discriminated using OPLS-DA analysis of both serum (p=0.033) and urinary (p<0.001) metabolome. The most highly weighted metabolites for these models included glucose, amino acids, lactate, and citrate. These findings suggest increased glycolysis, perturbation in the citrate cycle, oxidative stress, protein catabolism and increased urea cycle activity are key characteristics of newly presenting RA patients with elevated CRP.ConclusionsThis study consolidates our understanding of a previously identified relationship between serum metabolite profile and inflammation and provides novel evidence that there is a relationship between urinary metabolite profile and inflammation as measured by CRP. Identification of these metabolic perturbations provides insights into the pathogenesis of RA and may help in the identification of therapeutic targets.


2017 ◽  
Vol 64 (2) ◽  
Author(s):  
Nurul Shahfiza ◽  
Hasnah Osman ◽  
Tang Thean Hock ◽  
Abdel-Hamid Zaki Abdel-Hamid

Background: Dengue is one of the major public health problems in the world, affecting more than fifty million cases in tropical and subtropical region every year. The metabolome, as pathophysiological end-points, provide significant understanding of the mechanism and progression of dengue pathogenesis via changes in the metabolite profile of infected patients. Recent developments in diagnostic technologies provide metabolomics for the early detection of infectious diseases. Methods: The mid-stream urine was collected from 96 patients diagnosed with dengue fever at Penang General Hospital (PGH) and 50 healthy volunteers. Urine samples were analyzed with proton nuclear magnetic resonance (1H NMR) spectroscopy, followed by chemometric multivariate analysis. NMR signals highlighted in the orthogonal partial least square-discriminant analysis (OPLSDA) S-plots were selected and identified using Human Metabolome Database (HMDB) and Chenomx Profiler. A highly predictive model was constructed from urine profile of dengue infected patients versus healthy individuals with the total R2Y (cum) value 0.935, and the total Q2Y (cum) value 0.832. Results: Data showed that dengue infection is related to amino acid metabolism, tricarboxylic acid intermediates cycle and β-oxidation of fatty acids. Distinct variations in certain metabolites were recorded in infected patients including amino acids, various organic acids, betaine, valerylglycine, myoinositol and glycine. Conclusion: Metabolomics approach provides essential insight into host metabolic disturbances following dengue infection.


2021 ◽  
Author(s):  
Daniel Martins ◽  
Alessio Giacomel ◽  
Steven CR Williams ◽  
Federico E Turkheimer ◽  
Ottavia Dipasquale ◽  
...  

The expansion of neuroimaging techniques over the last decades has opened a wide range of new possibilities to characterize brain dysfunction in several neurological and psychiatric disorders. However, the lack of specificity of most of these techniques, such as magnetic resonance imaging (MRI)-derived measures, to the underlying molecular and cellular properties of the brain tissue poses limitations to the amount of information one can extract to inform precise models of brain disease. The integration of transcriptomic and neuroimaging data, known as 'imaging transcriptomics', has recently emerged as an indirect way forward to test and/or generate hypotheses about potential cellular and transcriptomic pathways that might underly specific changes in neuroimaging MRI biomarkers. However, the validity of this approach is yet to be examined in-depth. Here, we sought to bridge this gap by performing imaging transcriptomic analyses of the regional distribution of well-known molecular markers, assessed by positron emission tomography (PET), in the healthy human brain. We focused on tracers spanning different elements of the biology of the brain, including neuroreceptors, synaptic proteins, metabolism, and glia. Using transcriptome-wide data from the Allen Brain Atlas, we applied partial least square regression to rank genes according to their level of spatial alignment with the regional distribution of these neuroimaging markers in the brain. Then, we performed gene set enrichment analyses to explore the enrichment for specific biological and cell-type pathways among the genes most strongly associated with each neuroimaging marker. Overall, our findings show that imaging transcriptomics can recover plausible transcriptomic and cellular correlates of the regional distribution of benchmark molecular imaging markers, independently of the type of parcellation used to map gene expression and neuroimaging data. Our data support the plausibility and robustness of imaging transcriptomics as an indirect approach for bridging gene expression, cells and macroscopical neuroimaging and improving our understanding of the biological pathways underlying regional variability in neuroimaging features


Author(s):  
Vurayai Ruhanya ◽  
Graeme Brendon Jacobs ◽  
Robert Paul ◽  
John Joska ◽  
Soraya Seedat ◽  
...  

Background: HIV is accompanied by production of proinflammatory cytokines which are regarded as critical in neuronal damage, leading to brain dysfunction, hence the need to identify cytokine biomarkers sensitive to brain damage. Methods: We applied MRI volumetric neuroimaging and high throughput Luminex based immunoassays to examine the relationship between cortical white matter, subcortical gray matter and total gray matter brain volumes and plasma cytokines in HIV indviduals using generalised linear models and Partial least square regression model. Results: Higher plasma inflammatory cytokines CCL5/RANTES and MCP-1 were significantly associated with lower cortical white matter volume. Higher IL-6 was associated with both lower subcortical gray matter and lower total gray matter, whereas higher IL-8 and GM-CSF were associated with lower total gray matter only. Higher VEGF, PDGF-BB and IL-9 were associated with higher cortical white matter volumes. After standardisation and adjusting for clinical and demographic variables, IL-6, IL-8, MCP-1 remained associated with lower volumes of the three brain regions whereas IL-9, VEGF and PDGF-BB were associated with higher volumes. Conclusions: Association proinflammatory cytokines RANTES, MCP-1 and IL-6 with lower brain volumes could imply possible involvement in neurodegerative processes in HIV infection while IL-9, VEGF and PDGF may have a neuroprotective or neurotrophic role.


Molecules ◽  
2021 ◽  
Vol 26 (8) ◽  
pp. 2298
Author(s):  
Lavhelesani R. Managa ◽  
Elsa S. du Toit ◽  
Gerhard Prinsloo

Moringa oleifera Lam. is one of the world’s most useful medicinal plants. Different parts of the M. oleifera tree contain a rich profile of important minerals, proteins, vitamins, and various important bioactive compounds. However, there are differences in the phytochemical composition of the medicinal plant’s raw materials due to seasonal variation, cultivation practices, and post-harvest processing. The main objective of this study was therefore to determine the effect of harvesting frequencies on selected bioactive compounds of a M. oleifera cultivar (PKM1) grown in a hydroponic system under a shade net structure. Three harvesting frequency treatments were applied in the study, with the plants harvested at every 30 days (high frequency), 60 days (intermediate frequency), and 90 days (low frequency) respectively. 1H-NMR was used for data acquisition, and multivariate data analysis by means of principal component analysis (PCA), partial least square discriminatory analysis (PLS-DA), and orthogonal partial least square discriminatory analysis (OPLS-DA) were applied to determine the changes in the leaf metabolite profile, and also to identify the spectral features contributing to the separation of samples. Targeted metabolite analysis was used to match the NMR peaks of the compounds with the NMR chemical shifts of the contribution plot. The contribution plot showed that the increase in concentration of some compounds in aliphatic, sugar and aromatic regions contributed to the separation of the samples. The results revealed that intermediate and low harvesting frequencies resulted in a change in the leaf metabolite profile. Compounds such as chlorogenic acid, ferulic acid, vanillic acid, wogonin, esculetin, niazirin, and gamma-aminobutyric acid (GABA) showed an increase under intermediate and low harvesting frequencies. These results provide insight into the effect of harvesting frequencies on the metabolite profile and associated medicinal activity of M. oleifera.


2020 ◽  
Vol 28 (1) ◽  
pp. 71-88
Author(s):  
Tyas Tunjung Sari ◽  
Pandu Nuansa Luhur

This study aims to determine the motivation of work to mediate the effect of training and work environment on employee performance at PT. Telkom Witel Yogyakarta Yogyakarta. The purpose of this study is to determine and analyze 1) the effect of training on employee performance at PT. Telkom Witel Yogyakarta 2) the effect of training on employee performance through motivation at PT. Telkom Witel Yogyakarta 3) the influence of the work environment on employee performance at PT. Telkom Witel Yogyakarta 4) the influence of the work environment on employee performance through motivation at PT. Telkom Witel Yogyakarta. This study uses primary data through research on 62 respondents. Structural Equation is used to analyze data, using PLS (Partial Least Square) version 2.0. The results of this study indicate that there are 1) positive and significant influence of training on employee performance 2) positive and significant influence of work environment on employee performance 3) positive and significant effect of training on employee performance through motivation 4) positive and significant influence of work environment on employee performance through motivation.


2018 ◽  
Vol 16 (2) ◽  
pp. 113
Author(s):  
Sri Hastuti ◽  
Siti Sundari

Research Objectives to prove the influence of the complexity of the tasks faced by the Auditor on performance in carrying out duties as an Auditor. The complexity of tasks related to various problems in the company requires locus of control from internal and external to maintain independence and competence.The first auditor performance case occurred in 2002 with the disclosure of the Enron case involving the KAP in the big five, Athur Anderson. In 2008 the Telkom case affected the closure of KAP Edy Priyanto, and there were still many other cases which were violations of the accountant's code of ethics.This research is in the form of quantitative, with proof of the complexity of the task and locus of control on the performance of the auditor. Sample 46 Junior auditors from several KAPs in Surabaya, using the Partial Least Square test, the result that the complexity of the task affects the performance of the Auditor and the interaction of the complexity of the task with locus of control does not affect the performance of the Auditor.


2018 ◽  
Vol 3 (01) ◽  
pp. 45
Author(s):  
Nur Hidayat ◽  
Indah Kusuma Hayati

Recently, the evolvement of globalization era has been the global challenges that cannot be avoided either by private or government sectors, and they are requested to be survived encountering such the condition. The implementation of Quality Management System (QMS) in the operational company is the way how to guarantee the quality of products or services offered to the people. One of the purposes of QMS implementation is to provide a prime satisfaction to the customers. The impact of QMS implementation is expected to increase job performance of the employees. Besides the implementation of Quality Management System (QMS), the impact of global challenges has been increasing the competitive efforts to execute more effective production process. However, it has required manpower protection accordingly. This research aims to find out whether the implementation of quality management system and safety and healthy at work management system have impacted on the job performance of employees. Objects of this research are the employees in the production department at PT Guna Senaputra Sejahtera Plant 1 Bogor. Data analysis technique of this research has applied software Smart PLS (Partial Least Square). PLS has estimated a model of correlation among the latent variables and correlation between latent variables and its indicators. Result of data processing has indicated that the implementation of Quality Management System (QMS) and system of safety and healthy at work have positively and significantly impacted job performance of employees.Keywords : Quality Management System (QMS), Safety and Healthy at Work System ( SHWS / SMK3), and Job Performance of Employees


2020 ◽  
Vol 7 (2) ◽  
pp. 61-70
Author(s):  
Fachri Eka Saputra ◽  
Fedyah Anggriani

The purpose of this study as to determine how the effect of waterpark image and price fairness on customer satisfaction and its implications for customer loyalty at Waterpark Wahana Surya Bengkulu. The measurement of this study uses 14 indicator items which are distributed using an online questionnaire. The number of samples in this study were 136 respondents and the data were analyzed using SEM PLS (Partial Least Square). Date were collected using a questionnaire using a Likert scale. This research used descriptive method with a quantitative approach. The type of data used in this study is primary data. The results of this study prove that 1. waterpark image has a positive effect on price fairness, 2. Waterpark image has a positive effect on customer satisfaction, 3. Fairness of price has a positive effect on customer satisfaction, 4. Waterpark image has a positive effect on customer loyalty, 5. Fairness of price has a positive effect on customer loyalty, 6. Customer satisfaction has no effect on customer loyalty.


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