Integration of network pharmacology, metabolomics and lipidomics for clarifying the role of sphingolipid metabolism in the treatment of liver cancer by regorafenib.

Aims: Regorafenib, an FDA-approved drug for advanced primary liver cancer (PLC), could provide survival benefits for patients. However, markers for its therapeutic sensitivity are lacking. This study seeks to identify sensitive targets of regorafenib in PLC from the perspective of small molecular metabolites.

HIF-1α-HPRT1 axis promotes tumorigenesis and gefitinib resistance by enhancing purine metabolism in EGFR-mutant lung adenocarcinoma.

Background: The mutations of oncogenic epidermal growth factor receptor (EGFR) is an important cause of lung adenocarcinoma (LUAD) malignance. It has been knowm that metabolic reprogramming is an important hallmark of malignant tumors, and purine metabolism is a key metabolic pathway for tumor progression and drug resistance, but its relationship with the EGFR-mutant LUAD is unclear.

Methods: Metabolic reprogramming was studied through capillary electrophoresis-time of flight mass spectrometry (CE-TOF/MS)-based metabolic profiling analysis.

Polarization of Macrophages in Tumor Microenvironment Using High-Throughput Single-Cell Metabolomics.

Macrophages consist of a heterogeneous population of functionally distinct cells that participate in many physiological and pathological processes. They exhibit prominent plasticity by changing their different functional phenotypes represented by proinflammatory (M1) and anti-inflammatory (M2) in response to different environmental stimuli. Emerging evidence illustrates the importance of intracellular metabolic pathways in macrophage polarizations and functions.

Concentric Hybrid Nanoelectrospray Ionization-Atmospheric Pressure Chemical Ionization Source for High-Coverage Mass Spectrometry Analysis of Single-Cell Metabolomics.

High-coverage mass spectrometry analysis of single-cell metabolomics remains challenging due to the extremely low abundance and wide polarity of metabolites and ultra-small volume in single cells. Herein, a novel concentric hybrid ionization source, nanoelectrospray ionization-atmospheric pressure chemical ionization (nanoESI-APCI), is ingeniously designed to detect polar and nonpolar metabolites simultaneously in single cells. The source is constructed by inserting a pulled glass capillary coaxially into a glass tube that acts as a dielectric barrier layer.

High-sensitivity profiling of dipeptides in sauce-flavor Baijiu Daqu by chemical derivatization and ultrahigh-performance liquid chromatography coupled with high-resolution mass spectrometry.

Dipeptides in sauce-flavor Baijiu Daqu are protein degradation products during the fermentation of Daqu, which are believed to play a crucial role in the flavor and quality of Baijiu. Herein, we integrated dansyl chloride derivatization with ultrahigh-performance liquid chromatography coupled with high-resolution mass spectrometry (UHPLC-HRMS) for comprehensively profiling dipeptides in Daqu. The derivatization efficiency was higher than 99.

Oral micronized progesterone versus vaginal progesterone for luteal phase support in fresh embryo transfer cycles: a multicenter, randomized, non-inferiority trial.

Study Question: Does oral micronized progesterone result in a non-inferior ongoing pregnancy rate compared to vaginal progesterone gel as luteal phase support (LPS) in fresh embryo transfer cycles?

Summary Answer: The ongoing pregnancy rate in the group administered oral micronized progesterone 400 mg per day was non-inferior to that in the group administered vaginal progesterone gel 90 mg per day.

What Is Known Already: LPS is an integrated component of fresh IVF, for which an optimal treatment regimen is still lacking. The high cost and administration route of the commonly used vaginal progesterone make it less acceptable than oral micronized progesterone; however, the efficacy of oral micronized progesterone is unclear owing to concerns regarding its low bioavailability after the hepatic first pass.

Low Dose of 5-Aminolevulinic Acid Hydrochloride Alleviates the Damage in Cardiomyocytes Induced by Lenvatinib via PI3K/AKT Signaling Pathway.

Background: Lenvatinib is an oral tyrosine kinase inhibitor (TKI), and has been applied in the clinical trials for the treatment of hepatocellular carcinoma (HCC). The function of 5-aminolevulinic acid hydrochloride (ALA) treatment in protecting cardiomyocytes under lenvatinib stimulation was investigated.

Methods: H9c2 cells were treated with 2 mg/mL lenvatinib for 48 h and 1 mM ALA in the lenvatinib with low dose 5-aminolevulinic acid treatment group (LL) group, 10 mM ALA in the lenvatinib with high-dose 5-aminolevulinic acid treatment group (LH) group and cells without treatment were used as an internal control.

Profiling and annotation of carbonyl compounds in Baijiu Daqu by chlorine isotope labeling-assisted ultrahigh-performance liquid chromatography-high resolution mass spectrometry.

Carbonyl compounds are among the most important flavor substances that affect the taste of Baijiu. However, high coverage analysis of carbonyl compounds is obstructed due to the poor ionization efficiency of these compounds. Here we report a chlorine isotope labeling-assisted ultrahigh-performance liquid chromatography-high resolution mass spectrometry-based method (CIL-UHPLCHRMS) for profiling and annotation of carbonyl compounds in sauce flavored-Baijiu Daqu.

Ex vivo instability of lipids in whole blood: preanalytical recommendations for clinical lipidomics studies.

Reliability, robustness, and interlaboratory comparability of quantitative measurements is critical for clinical lipidomics studies. Lipids' different ex vivo stability in blood bears the risk of misinterpretation of data. Clear recommendations for the process of blood sample collection are required.

Steroid profiling for the diagnosis of congenital adrenal hyperplasia by microbore ultra-performance liquid chromatography-tandem mass spectrometry.

Background: A rapid and accurate measurement approach for 17α-hydroxyprogesterone (17-OHP) and related steroids in amount/volume-limited clinic samples is of importance for precise newborn diagnosis of congenital adrenal hyperplasia (CAH) and its subtypes in clinic.

Methods: Sixteen steroids (17-OHP, androstenedione, cortisol, tetrahydro-11-deoxycortisol, pregnenolone, progesterone, 11-deoxycorticosterone, corticosterone, 21-deoxycortisol, 11-deoxycortisol, dehydroepiandrosterone, testosterone, aldosterone, 17α-hydroxypregnenolone, dihydrotestosterone and 18-hydroxycorticosterone) were included in the panel of high-throughput microbore ultra-performance liquid chromatography-tandem mass spectrometry. Samples were collected from 126 normal subjects and 65 patients including different subtypes of CAH.

Chinese expert consensus on the diagnosis and treatment of thymic epithelial tumors.

Thymic epithelial tumors (TETs) are a relatively rare type of thoracic tumor, accounting for less than 1% of all tumors. The incidence of TETs is about 3.93/10000 in China, slightly higher than that of European and American countries.

Effect of roxadustat on serum metabolome and lipidome in patients with end-stage renal disease and erythropoiesis-stimulating agent resistance.

Background: Roxadustat is a newly marketed hypoxia-inducible factor prolyl hydroxylase inhibitor used to treat anemia in patients with end-stage renal disease (ESRD). While clinical trials have demonstrated the therapeutic effects of roxadustat in patients with ESRD who are resistant to erythropoiesis-stimulating agents (ESAs), its metabolic effects are still unclear.

Methods: Thirty-two individuals with ESRD and ESA resistance from the Blood Purification Center of Dalian Municipal Central Hospital were included.

Defect in Ser312 phosphorylation of Tp53 dysregulates lipid metabolism for fatty accumulation and fatty liver susceptibility: Revealed by lipidomics.

The Tp53 gene is a well-known tumour suppressor, mutation of which (e.g. prevention of Ser312 phosphorylation) induces deletion or expression of an inactive p53 protein to increase the susceptibility of tumour occurance.

Serum lipidomics profiles reveal potential lipid markers for prediabetes and type 2 diabetes in patients from multiple communities.

Objective: Dyslipidemia is a hallmark of diabetes mellitus (DM). However, specific lipid molecules closely associated with the initiation and progression of diabetes remain unclear. We used a pseudotargeted lipidomics approach to evaluate the complex lipid changes that occurred long before the diagnosis of type 2 diabetes mellitus (T2DM) and to identify novel lipid markers for screening prediabetes mellitus (PreDM) and T2DM in patients from multiple communities.

Medium-chain triglyceride production in Nannochloropsis via a fatty acid chain length discriminating mechanism.

Depending on their fatty acid (FA) chain length, triacylglycerols (TAGs) have distinct applications; thus, a feedstock with a genetically designed chain length is desirable to maximize process efficiency and product versatility. Here, ex vivo, in vitro, and in vivo profiling of the large set of type-2 diacylglycerol acyltransferases (NoDGAT2s) in the industrial oleaginous microalga Nannochloropsis oceanica revealed two endoplasmic reticulum-localized enzymes that can assemble medium-chain FAs (MCFAs) with 8-12 carbons into TAGs. Specifically, NoDGAT2D serves as a generalist that assembles C8-C18 FAs into TAG, whereas NoDGAT2H is a specialist that incorporates only MCFAs into TAG.

High-throughput single cell metabolomics and cellular heterogeneity exploration by inertial microfluidics coupled with pulsed electric field-induced electrospray ionization-high resolution mass spectrometry.

Single cell metabolomics can obtain the metabolic profiles of individual cells and reveal cellular heterogeneity. However, high-throughput single-cell mass spectrometry (MS) analysis under physiological conditions remains a great challenge due to the presence of complex matrix and extremely small cell volumes. Herein, a serpentine channel microfluidic device which was designed to achieve continuous cell separation and inertial focusing, was coupled with a pulsed electric field-induced electrospray ionization-high resolution MS (PEF-ESI-HRMS) to achieve high-throughput single cell analysis.

Strategy for Nontargeted Metabolomic Annotation and Quantitation Using a High-Resolution Spectral-Stitching Nanoelectrospray Direct-Infusion Mass Spectrometry with Data-Independent Acquisition.

Direct-infusion nanoelectrospray ionization high-resolution mass spectrometry (DI-nESI-HRMS) is an alternative approach to chromatography-MS-based techniques for nontargeted metabolomics, offering a high sample throughout. However, its annotation accuracy of analytes is still full of challenges. In this study, we proposed a strategy for the annotation and quantitation of nontargeted metabolomic data using a spectral-stitching DI-nESI-HRMS with data-independent acquisition.

Lipid Profiling of 20 Mammalian Cells by Capillary Microsampling Combined with High-Resolution Spectral Stitching Nanoelectrospray Ionization Direct-Infusion Mass Spectrometry.

Studies of cellular metabolism can provide profound insights into the underlying molecular mechanisms and metabolic function. To date, the majority of cellular metabolism studies based on chromatography-mass spectrometry (MS) require population cells to obtain informative metabolome. These methods are not only time-consuming but also not suitable for amount-limited cell samples such as circulating tumor cells, stem cells, and neurons.

A high throughput lipidomics method and its application in atrial fibrillation based on 96-well plate pretreatment and liquid chromatography-mass spectrometry.

Successful applications of lipidomics in clinic need study large-scale samples, and the bottlenecks are in throughput and robustness of the lipid analytical method. Here, we report an untargeted lipidomics method by combining high throughput pretreatment in the 96-well plate with ultra-high performance liquid chromatography coupled to quadrupole time-of-flight tandem mass spectrometry. The developed method was validated to have satisfactory analytical characteristics in terms of linearity, repeatability and extraction recovery.

miR-133b inhibits cell proliferation, migration, and invasion of lung adenocarcinoma by targeting CDCA8.

Objective: Lung adenocarcinoma (LUAD) is the most common type of lung cancer. This study aims to explore the mechanism by which CDCA8 regulates cell proliferation, invasion, and migration of LUAD, and to generate novel insights into targeted therapy of LUAD.

Methods: Expression profiles of mature microRNAs (miRNAs) and mRNAs, along with clinical data of LUAD were downloaded from TCGA database for differential analysis and survival analysis to mine differentially expressed mRNAs.

Metabolic Alterations Related to Glioma Grading Based on Metabolomics and Lipidomics Analyses.

Gliomas are the most aggressive phenotypes of brain tumors and are classified into four grades according to the malignancy degree by the World Health Organization. Metabolic profiling can provide an overview of metabolic reprogramming at a specific stage of tumor initiation and development. Studies about metabolic alterations related to different grades of gliomas are helpful to understand the molecular mechanism for progression of glioma.

Multiplatform Metabolomics Reveals Novel Serum Metabolite Biomarkers in Diabetic Retinopathy Subjects.

Diabetic retinopathy (DR) is the main cause of vision loss or blindness in working age adults worldwide. The lack of effective diagnostic biomarkers for DR leads to unsatisfactory curative treatments. To define potential metabolite biomarkers for DR diagnosis, a multiplatform-based metabolomics study is performed.

Recent advances in analytical strategies for mass spectrometry-based lipidomics.

Lipids are vital biological molecules and play multiple roles in cellular function of mammalian organisms such as cellular membrane anchoring, signal transduction, material trafficking and energy storage. Driven by the biological significance of lipids, lipidomics has become an emerging science in the field of omics. Lipidome in biological systems consists of hundreds of thousands of individual lipid molecules that possess complex structures, multiple categories, and diverse physicochemical properties assembled by different combinations of polar headgroups and hydrophobic fatty acyl chains.