scholarly journals A non-targeted LC–MS metabolic profiling of pregnancy: longitudinal evidence from healthy and pre-eclamptic pregnancies

Metabolomics ◽  
2021 ◽  
Vol 17 (2) ◽  
Author(s):  
Tiina Jääskeläinen ◽  
◽  
Olli Kärkkäinen ◽  
Jenna Jokkala ◽  
Anton Klåvus ◽  
...  
Keyword(s):  
Large Scale ◽  
Scale Effects ◽  
Late Pregnancy ◽  
Metabolite Profile ◽  
Adverse Outcomes ◽  
Liquid Chromatography Mass Spectrometry ◽  
Targeted Metabolomics ◽  
Serum Samples ◽  
Healthy Women ◽  
Maternal Metabolism

Abstract Introduction Maternal metabolism changes substantially during pregnancy. However, few studies have used metabolomics technologies to characterize changes across gestation. Objectives and methods We applied liquid chromatography–mass spectrometry (LC–MS) based non-targeted metabolomics to determine whether the metabolic profile of serum differs throughout the pregnancy between pre-eclamptic and healthy women in the FINNPEC (Finnish Genetics of Preeclampsia Consortium) Study. Serum samples were available from early and late pregnancy. Results Progression of pregnancy had large-scale effects to the serum metabolite profile. Altogether 50 identified metabolites increased and 49 metabolites decreased when samples of early pregnancy were compared to samples of late pregnancy. The metabolic signatures of pregnancy were largely shared in pre-eclamptic and healthy women, only urea, monoacylglyceride 18:1 and glycerophosphocholine were identified to be increased in the pre-eclamptic women when compared to healthy controls. Conclusions Our study highlights the need of large-scale longitudinal metabolomic studies in non-complicated pregnancies before more detailed understanding of metabolism in adverse outcomes could be provided. Our findings are one of the first steps for a broader metabolic understanding of the physiological changes caused by pregnancy per se.

scholarly journals A pilot study of discovery and validation of peritoneal endometriosis biomarkers in peritoneal fluid and serum

2020 ◽  
Author(s):  
See Ling Loy ◽  
Jieliang Zhou ◽  
Liang Cui ◽  
Tse Yeun Tan ◽  
Tat Xin Ee ◽  
...  
Keyword(s):  
Peritoneal Fluid ◽  
Liquid Chromatography Mass Spectrometry ◽  
Operating Characteristics ◽  
Targeted Metabolomics ◽  
Serum Samples ◽  
Pilot Studies ◽  
Potential Biomarker ◽  
Receiver Operating Characteristics Curve ◽  
Peritoneal Endometriosis ◽  
Validation Set

ObjectiveTo identify potential serum biomarkers in women with peritoneal endometriosis (PE) by first looking at its source in the peritoneal fluid (PF).DesignCase-control pilot studies, comprising independent discovery and validation sets.SettingKK Women’s and Children’s Hospital, Singapore.Patient(s)Women with laparoscopically confirmed PE and absence of endometriosis (control).Intervention(s)None.Main Outcome Measure(s)In the discovery set, we used untargeted liquid chromatography-mass spectrometry (LC-MS/MS) metabolomics, multivariable and univariable analyses to generate global metabolomic profiles of PF for endometriosis and to identify potential metabolites that could distinguish PE (n=10) from controls (n=31). Using targeted metabolomics, we validated the identified metabolites in PF and sera of cases (n=16 PE) and controls (n=19). We performed the area under the receiver-operating characteristics curve (AUC) analysis to evaluate the diagnostic performance of PE metabolites.Result(s)In the discovery set, PF phosphatidylcholine (34:3) and phenylalanyl-isoleucine were significantly increased in PE than controls groups, with AUC 0.77 (95% confidence interval 0.61-0.92; p=0.018) and AUC 0.98 (0.95-1.02; p<0.001), respectively. In the validation set, phenylalanyl-isoleucine retained discriminatory performance to distinguish PE from controls in both PF (AUC 0.77; 0.61-0.92; p=0.006) and serum samples (AUC 0.81; 0.64-0.99; p=0.004).Conclusion(s)Our preliminary results propose phenylalanyl-isoleucine as a potential biomarker of PE, which may be used as a minimally-invasive diagnostic biomarker of PE.

scholarly journals Untargeted Metabolomics and Polyamine Profiling in Serum before and after Surgery in Colorectal Cancer Patients

Metabolites ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. 487
Author(s):  
Yu Ra Lee ◽  
Ki-Yong An ◽  
Justin Jeon ◽  
Nam Kyu Kim ◽  
Ji Won Lee ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metabolic Pathways ◽  
Sphingolipid Metabolism ◽  
Proline Metabolism ◽  
Liquid Chromatography Mass Spectrometry ◽  
Targeted Metabolomics ◽  
Serum Samples ◽  
Physiological Alterations ◽  
Before And After ◽  
Colorectal Cancer Patients

Colorectal cancer is one of the most prevalent cancers in Korea and globally. In this study, we aimed to characterize the differential serum metabolomic profiles between pre-operative and post-operative patients with colorectal cancer. To investigate the significant metabolites and metabolic pathways associated with colorectal cancer, we analyzed serum samples from 68 patients (aged 20–71, mean 57.57 years). Untargeted and targeted metabolomics profiling in patients with colorectal cancer were performed using liquid chromatography-mass spectrometry. Untargeted analysis identified differences in sphingolipid metabolism, steroid biosynthesis, and arginine and proline metabolism in pre- and post-operative patients with colorectal cancer. We then performed quantitative target profiling of polyamines, synthesized from arginine and proline metabolism, to identify potential polyamines that may serve as effective biomarkers for colorectal cancer. Results indicate a significantly reduced serum concentration of putrescine in post-operative patients compared to pre-operative patients. Our metabolomics approach provided insights into the physiological alterations in patients with colorectal cancer after surgery.

Strategies for large-scale targeted metabolomics quantification by liquid chromatography-mass spectrometry

The Analyst ◽  
2016 ◽  
Vol 141 (23) ◽  
pp. 6362-6373 ◽  
Author(s):  
Juntuo Zhou ◽  
Yuxin Yin
Keyword(s):  
Mass Spectrometry ◽  
Liquid Chromatography ◽  
Large Scale ◽  
Liquid Chromatography Mass Spectrometry ◽  
Targeted Metabolomics ◽  
Chromatography Mass Spectrometry ◽  
Great Progress ◽  
Analytical Strategies ◽  
Metabolomics Analysis

Advances in liquid chromatography-mass spectrometry (LC-MS) instruments and analytical strategies have brought about great progress in targeted metabolomics analysis.

scholarly journals European Biological Variation Study (EuBIVAS): within- and between-subject biological variation estimates for serum thyroid biomarkers based on weekly samplings from 91 healthy participants

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Michela Bottani ◽  
Aasne K. Aarsand ◽  
Giuseppe Banfi ◽  
Massimo Locatelli ◽  
Abdurrahman Coşkun ◽  
...  
Keyword(s):  
Large Scale ◽  
Thyroid Stimulating Hormone ◽  
Biological Variation ◽  
Healthy Individuals ◽  
Serum Samples ◽  
Free Triiodothyronine ◽  
Performance Specifications ◽  
Study Population ◽  
Variance Homogeneity ◽  
Healthy Participants

Abstract Objectives Thyroid biomarkers are fundamental for the diagnosis of thyroid disorders and for the monitoring and treatment of patients with these diseases. The knowledge of biological variation (BV) is important to define analytical performance specifications (APS) and reference change values (RCV). The aim of this study was to deliver BV estimates for thyroid stimulating hormone (TSH), free thyroxine (FT4), free triiodothyronine (FT3), thyroglobulin (TG), and calcitonin (CT). Methods Analyses were performed on serum samples obtained from the European Biological Variation Study population (91 healthy individuals from six European laboratories; 21–69 years) on the Roche Cobas e801 at the San Raffaele Hospital (Milan, Italy). All samples from each individual were evaluated in duplicate within a single run. The BV estimates with 95% CIs were obtained by CV-ANOVA, after analysis of variance homogeneity and outliers. Results The within-subject (CV I ) BV estimates were for TSH 17.7%, FT3 5.0%, FT4 4.8%, TG 10.3, and CT 13.0%, all significantly lower than those reported in the literature. No significant differences were observed for BV estimates between men and women. Conclusions The availability of updated, in the case of CT not previously published, BV estimates for thyroid markers based on the large scale EuBIVAS study allows for refined APS and associated RCV applicable in the diagnosis and management of thyroid and related diseases.

scholarly journals Low seroprevalence rates of Zika virus in Kuala Lumpur, Malaysia

2019 ◽  
Vol 113 (11) ◽  
pp. 678-684 ◽  
Author(s):  
I-Ching Sam ◽  
Magelda Montoya ◽  
Chong Long Chua ◽  
Yoke Fun Chan ◽  
Andrew Pastor ◽  
...  
Keyword(s):  
Zika Virus ◽  
Large Scale ◽  
Binding Assay ◽  
Seroprevalence Rate ◽  
Protective Effects ◽  
Kuala Lumpur ◽  
Serum Samples ◽  
Denv Serotypes ◽  
Population Immunity ◽  
Low Incidence

Abstract Background Zika virus (ZIKV) is believed to be endemic in Southeast Asia. However, there have been few Zika cases reported to date in Malaysia, which could be due to high pre-existing levels of population immunity. Methods To determine Zika virus (ZIKV) seroprevalence in Kuala Lumpur, Malaysia, 1085 serum samples from 2012, 2014–2015 and 2017 were screened for anti-ZIKV antibodies using a ZIKV NS1 blockade-of-binding assay. Reactive samples were confirmed using neutralization assays against ZIKV and the four dengue virus (DENV) serotypes. A sample was possible ZIKV seropositive with a ZIKV 50% neutralization (NT50) titre ≥20. A sample was probable ZIKV seropositive if, in addition, all DENV NT50 titres were &lt;20 or the ZIKV NT50 titre was &gt;4-fold greater than the highest DENV NT50 titre. Results We found low rates of possible ZIKV seropositivity (3.3% [95% confidence interval {CI} 2.4 to 4.6]) and probable ZIKV seropositivity (0.6% [95% CI 0.3 to 1.4]). Possible ZIKV seropositivity was independently associated with increasing age (odds ratio [OR] 1.04 [95% CI 1.02 to 1.06], p&lt;0.0001) and male gender (OR 3.5 [95% CI 1.5 to 8.6], p=0.005). Conclusions The low ZIKV seroprevalence rate, a proxy for population immunity, does not explain the low incidence of Zika in dengue-hyperendemic Kuala Lumpur. Other factors, such as the possible protective effects of pre-existing flavivirus antibodies or reduced transmission by local mosquito vectors, should be explored. Kuala Lumpur is at high risk of a large-scale Zika epidemic.

PD-L1 expression in tumor lesions and soluble PD-L1 serum levels in patients with breast cancer: TNBC versus TPBC

2021 ◽  
pp. 1-9
Author(s):  
Parvaneh Yazdanpanah ◽  
Ali Alavianmehr ◽  
Abbas Ghaderi ◽  
Ahmad Monabati ◽  
Mehdi Montazer ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Cells ◽  
Serum Levels ◽  
Tumor Stage ◽  
Serum Samples ◽  
Healthy Women ◽  
Grade 3 ◽  
Anti Tumor Activity ◽  
Tnbc Subtype ◽  
Cell Death Protein

BACKGROUND: Block of programmed cell death protein 1 (PD-1) interaction with its ligand, PD-L1, enhances anti-tumor activity. OBJECTIVES: We aimed to assess the association between PD-L1 expression in tumor cells and CD8+ tumor infiltrating T cells (TILs) as well as soluble (s)PD-L1 serum levels in patients with triple negative breast cancer (TNBC) compared to triple positive (TPBC). METHODS: A total of 113 tumor sections and 133 serum samples were available from 144 patients with breast cancer (72 TNBC and 72 TPBC). Dual immunohistochemistry staining was applied to determine differential PD-L1 expression in tumor cells and CD8+ TILs. Soluble PD-L1 serum levels were also evaluated in patients compared to 40 healthy women by ELISA method. RESULTS: Despite TPBC patients which were mostly grades 1/2, TNBC patients were grade 3 (72% versus 66.7%, P < 0.001). Most of the TNBC patients were stages I/II, whereas most of the TPBC patients were stages III/IV (57.3% versus 68.3%,P = 0.005). There was no difference in tumor size and metastasis between TNBC and TPBC patients, although the number of involved lymph nodes was significantly more in TPBC patients (P = 0.0012). PD-L1 expression was detected in 11.5% of samples mostly in TNBC subtype and was associated with advanced grades (P = 0.039). There was no relationship between PD-L1 expression and tumor stage. PD-L1 expression in CD8+ TILs was nonsignificantly higher than tumor cells. Serum levels of sPD-L1 showed no difference between patients and healthy women. We found no correlation between PD-L1 expression in tumor lesions and serum levels of sPD-L1 in patients. CONCLUSION: PD-L1 expression was more detected in our patients with TNBC. It seems that, these patients who are resistant to standard chemotherapy regimens may get benefit from PD-L1 inhibition therapy and because of its low serum levels, sPD-L1 cannot interfere with this therapy.

scholarly journals Glucose-Limited Fed-Batch Cultivation Strategy to Mimic Large-Scale Effects in Escherichia coli Linked to Accumulation of Non-Canonical Branched-Chain Amino Acids by Combination of Pyruvate Pulses and Dissolved Oxygen Limitation

2021 ◽  
Vol 9 (6) ◽  
pp. 1110
Author(s):  
Ángel Córcoles García ◽  
Peter Hauptmann ◽  
Peter Neubauer
Keyword(s):  
Amino Acids ◽  
Dissolved Oxygen ◽  
Large Scale ◽  
Scale Effects ◽  
Branched Chain Amino Acids ◽  
Oxygen Limitation ◽  
Fed Batch ◽  
Fermentation Products ◽  
Cultivation Strategy ◽  
Branched Chain

Insufficient mixing in large-scale bioreactors provokes gradient zones of substrate, dissolved oxygen (DO), pH, and other parameters. E. coli responds to a high glucose, low oxygen feeding zone with the accumulation of mixed acid fermentation products, especially formate, but also with the synthesis of non-canonical amino acids, such as norvaline, norleucine and β-methylnorleucine. These amino acids can be mis-incorporated into recombinant products, which causes a problem for pharmaceutical production whose solution is not trivial. While these effects can also be observed in scale down bioreactor systems, these are challenging to operate. Especially the high-throughput screening of clone libraries is not easy, as fed-batch cultivations would need to be controlled via repeated glucose pulses with simultaneous oxygen limitation, as has been demonstrated in well controlled robotic systems. Here we show that not only glucose pulses in combination with oxygen limitation can provoke the synthesis of these non-canonical branched-chain amino acids (ncBCAA), but also that pyruvate pulses produce the same effect. Therefore, we combined the enzyme-based glucose delivery method Enbase® in a PALL24 mini-bioreactor system and combined repeated pyruvate pulses with simultaneous reduction of the aeration rate. These cultivation conditions produced an increase in the non-canonical branched chain amino acids norvaline and norleucine in both the intracellular soluble protein and inclusion body fractions with mini-proinsulin as an example product, and this effect was verified in a 15 L stirred tank bioreactor (STR). To our opinion this cultivation strategy is easy to apply for the screening of strain libraries under standard laboratory conditions if no complex robotic and well controlled parallel cultivation devices are available.

CPVA: a web-based metabolomic tool for chromatographic peak visualization and annotation

2020 ◽  
Vol 36 (12) ◽  
pp. 3913-3915
Author(s):  
Hemi Luan ◽  
Xingen Jiang ◽  
Fenfen Ji ◽  
Zhangzhang Lan ◽  
Zongwei Cai ◽  
...  
Keyword(s):  
False Positive ◽  
Supplementary Information ◽  
Liquid Chromatography Mass Spectrometry ◽  
Targeted Metabolomics ◽  
Metabolomics Data ◽  
Web Based ◽  
Tremendous Amount ◽  
Chromatographic Peaks ◽  
User Friendly

Abstract Motivation Liquid chromatography–mass spectrometry-based non-targeted metabolomics is routinely performed to qualitatively and quantitatively analyze a tremendous amount of metabolite signals in complex biological samples. However, false-positive peaks in the datasets are commonly detected as metabolite signals by using many popular software, resulting in non-reliable measurement. Results To reduce false-positive calling, we developed an interactive web tool, termed CPVA, for visualization and accurate annotation of the detected peaks in non-targeted metabolomics data. We used a chromatogram-centric strategy to unfold the characteristics of chromatographic peaks through visualization of peak morphology metrics, with additional functions to annotate adducts, isotopes and contaminants. CPVA is a free, user-friendly tool to help users to identify peak background noises and contaminants, resulting in decrease of false-positive or redundant peak calling, thereby improving the data quality of non-targeted metabolomics studies. Availability and implementation The CPVA is freely available at http://cpva.eastus.cloudapp.azure.com. Source code and installation instructions are available on GitHub: https://github.com/13479776/cpva. Supplementary information Supplementary data are available at Bioinformatics online.

scholarly journals Integrated Transcriptomic and Un-Targeted Metabolomics Analysis Reveals Mulberry Fruit (Morus atropurpurea) in Response to Sclerotiniose Pathogen Ciboria shiraiana Infection

2020 ◽  
Vol 21 (5) ◽  
pp. 1789 ◽  
Author(s):  
Lijun Bao ◽  
Hongpeng Gao ◽  
Zelin Zheng ◽  
Xiaoxiao Zhao ◽  
Minjuan Zhang ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Early Stage ◽  
Metabolite Profile ◽  
Northwest China ◽  
Targeted Metabolomics ◽  
Mulberry Fruit ◽  
Phenylpropanoid Biosynthesis ◽  
Mapman Analysis ◽  
Mulberry Fruits ◽  
Prevention Methods

Mulberry sclerotiniose caused by Ciboria shiraiana is a devastating disease of mulberry (Morus alba L.) fruit in Northwest China. At present, no disease-resistant varieties are used in production, as the molecular mechanisms of this disease are not well understood. In this study, to explore new prevention methods and provide direction for molecular breeding, transcriptomic sequencing and un-targeted metabolomics were performed on healthy (CK), early-stage diseased (HB1), and middle-stage diseased (HB2) mulberry fruits. Functional annotation, gene ontology, a Kyoto encyclopedia of genes and genomes (KEGG) analysis, and a Mapman analysis of the differentially expressed genes revealed differential regulation of genes related to plant hormone signal transduction, transcription factors, and phenylpropanoid biosynthesis. A correspondence between the transcript pattern and metabolite profile was observed in the phenylpropanoid biosynthesis pathway. It should be noted that the log2 ratio of eugenol (isoeugenol) in HB1 and HB2 are 85 times and 23 times higher than CK, respectively. Our study shows that phenylpropanoid biosynthesis may play an essential role in response to sclerotiniose pathogen infection and eugenol(isoeugenol) enrichment in mulberry fruit, which may provide a novel method for mulberry sclerotiniose control.

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