Exploring neuron-specific steroid synthesis and DHEAS therapy in Alzheimer's disease.

Alzheimer's Disease (AD) is a neurodegenerative disorder characterized by cognitive decline and memory loss. Recent studies have suggested a potential role for steroid synthesis in AD pathology. This study investigated the co-localization of steroidogenic enzymes in neuronal cells, changes in enzyme expression in an AD mouse model, and steroid expressions in human AD samples.

Rapid Screening of New Psychoactive Substances Using pDART-QqQ-MS.

Drug abuse is a severe social problem worldwide. Particularly, the issue of new psychoactive substances (NPSs) have increasingly emerged. NPSs are structural or functional analogs of traditional illicit drugs, such as cocaine, cannabis, and amphetamine; these molecules provide the same or more severe neurological effects.

Hepatoviruses promote very-long-chain fatty acid and sphingolipid synthesis for viral RNA replication and quasi-enveloped virus release.

Virus-induced changes in host lipid metabolism are an important but poorly understood aspect of viral pathogenesis. By combining nontargeted lipidomics analyses of infected cells and purified extracellular quasi-enveloped virions with high-throughput RNA sequencing and genetic depletion studies, we show that hepatitis A virus, an hepatotropic picornavirus, broadly manipulates the host cell lipid environment, enhancing synthesis of ceramides and other sphingolipids and transcriptionally activating acyl-coenzyme A synthetases and fatty acid elongases to import and activate long-chain fatty acids for entry into the fatty acid elongation cycle. Phospholipids with very-long-chain acyl tails (>C22) are essential for genome replication, whereas increases in sphingolipids support assembly and release of quasi-enveloped virions wrapped in membranes highly enriched for sphingomyelin and very-long-chain ceramides.

Optimizing adrenal vein sampling in primary aldosteronism subtyping through LC-MS/MS and secretion ratios of aldosterone, 18-oxocortisol, and 18-hydroxycortisol.

Adrenal venous sampling (AVS) is the gold standard for identifying curable unilateral aldosterone excess in primary aldosteronism (PA). Studies have demonstrated the value of steroid profiling through liquid chromatography-tandem mass spectrometry (LC-MS/MS) in AVS interpretation. First, the performance of LC-MS/MS and immunoassay in assessing selectivity and lateralization was compared.

MetaMOPE: a web service for mobile phase determination and fast chromatography peaks evaluation for metabolomics.

Motivation: Liquid chromatography coupled with mass spectrometry (LC-MS) is widely used in metabolomics studies, while HILIC LC-MS is particularly suited for polar metabolites. Determining an optimized mobile phase and developing a proper liquid chromatography method tend to be laborious, time-consuming and empirical.

Results: We developed a containerized web tool providing a workflow to quickly determine the optimized mobile phase by batch-evaluating chromatography peaks for metabolomics LC-MS studies.

[Latest Findings on the Interaction Mechanism Between Depressive Disorder and Intestinal Permeability].

The intestinal barrier, a complex structure consisting of multiple layers of defense barriers, blocks the transfer of intestinal and foreign bacteria and their metabolites into the internal environment of the human body. Intestinal permeability can be used to evaluate the integrity of the intestinal barrier. Increased intestinal permeability has been observed in patients with depressive disorder.

Determining plasma and cerebrospinal fluid concentrations of EGFR-TKI in lung cancer patients.

Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are commonly used to treat advanced non-small cell lung cancer (NSCLC). A rapid and reliable method for measuring plasma and cerebrospinal fluid (CSF) concentrations of EGFR-TKIs is needed for therapeutic drug monitoring. By using UHPLC‒MS/MS with multiple reaction monitoring mode, we developed a method for rapidly determining the plasma and CSF concentrations of gefitinib, erlotinib, afatinib, and osimertinib.

An automated workflow on data processing (AutoDP) for semiquantitative analysis of urine organic acids with GC-MS to facilitate diagnosis of inborn errors of metabolism.

Determination of urine organic acids (UOAs) is essential to understand the disease progress of inborn errors of metabolism (IEM) and often relies on GC-MS analysis. However, the efficiency of analytical reports is sometimes restricted by data processing due to labor-intensive work if no proper tool is employed. Herein, we present a simple and rapid workflow with an R-based script for automated data processing (AutoDP) of GC-MS raw files to quantitatively analyze essential UOAs.

Development of the dried blood spot preparation protocol for comprehensive evaluation of the hematocrit effect.

The application of dried blood spots (DBS) has gradually increased in different fields because of its several advantages. The hematocrit (Hct) effect is one major analytical challenge that may affect the quantification accuracy of DBS samples and should be investigated when developing a novel DBS method. However, previous studies usually overlooked the Hct-related distribution bias when evaluating the Hct effect.

Defective determination of synthetic cathinones in blood for forensic investigation.

Antemortem specimens are sometimes the sole sources available for forensic investigation, and samples collected in nonideal ways are inevitably employed to achieve toxicological analysis. It is essential to assess the effects of blood collection tubes on the recoveries of emerging synthetic cathinones (SC) to estimate actual drug concentrations, and no such systematic investigations have been previously carried out. Seventy-one SC with various LogP values were employed to examine commonly used blood collection tubes, including plasma tubes, serum tubes and gel-containing tubes in recoveries which determined by a reliable LC-MS/MS method.

Trastuzumab resistance in HER2-positive breast cancer: Mechanisms, emerging biomarkers and targeting agents.

Trastuzumab is a standard molecular targeted therapy for human epidermal growth factor receptor 2(HER2) -positive breast cancer, which can significantly improve the survival of patients with this molecular subtype of breast cancer. However, the clinical problem of onset or secondary resistance to trastuzumab has limited its efficacy. Therefore, it is very important to explore the mechanism of trastuzumab resistance and formulate countermeasures.

Development of an analytical method to detect simultaneously 219 new psychoactive substances and 65 other substances in urine specimens using LC-QqQ MS/MS with CriticalPairFinder and TransitionFinder.

Emerging new psychoactive substances (NPS) poses a great risk to public health. Analyzing these large numbers of NPS and other associated substances often relies on liquid chromatography coupled to triple quadrupole mass spectrometry (LC-QqQ-MS) with multiple-reaction monitoring (MRM) mode. However, the differentiation of critical pairs, coeluted isobaric and/or isomeric species, is one of the challenges for this analytical platform.

Activation of PPARα-catalase pathway reverses alcoholic liver injury via upregulating NAD synthesis and accelerating alcohol clearance.

Alcohol metabolism in the liver simultaneously generates toxic metabolites and disrupts redox balance, but the regulatory mechanisms have not been fully elucidated. The study aimed to characterize the role of PPARα in alcohol detoxification. Hepatic PPARα and catalase levels were examined in patients with severe alcoholic hepatitis.

17β-estradiol induces temozolomide resistance through NRF2-mediated redox homeostasis in glioblastoma.

Glioblastoma multiforme (GBM) is the most fatal cancer among brain tumors, and the standard treatment of GBM patients is surgical tumor resection followed by radiotherapy and temozolomide (TMZ) chemotherapy. However, tumors always recur due to the developing drug resistance. It has been shown that neurosteroids, including dehydroepiandrosterone and 17β-estradiol, are synthesized in TMZ-resistant GBM tumors.

Quantification of Plasma Oxylipins Using Solid-Phase Extraction and Reversed-Phase Liquid Chromatography-Triple Quadrupole Mass Spectrometry.

Oxylipins are an important class of bioactive lipids derived from polyunsaturated fatty acids. They can be both pro- and anti-inflammatory and function as important mediators in various pathological conditions. However, comprehensive analysis of oxylipins still remains a challenge because of their low abundance in plasma and the dominance of structurally similar isomeric species.

Using matrix-induced ion suppression combined with LC-MS/MS for quantification of trimethylamine-N-oxide, choline, carnitine and acetylcarnitine in dried blood spot samples.

Recently, there has been significant interest in the influences of the human gut microbiota on many diseases, such as cardiovascular disease (CVD) and metabolic disorders. Trimethylamine N-oxide (TMAO) is one of the most frequently discussed gut-derived metabolites. Dried blood spot (DBS) sampling has been regarded as an attractive alternative sampling strategy for clinical studies and offers many advantages.

Blueberry and/or Banana Consumption Mitigate Arachidonic, Cytochrome P450 Oxylipin Generation During Recovery From 75-Km Cycling: A Randomized Trial.

Oxylipins are bioactive lipid oxidation products, have vital regulatory roles in numerous physiological processes including inflammation, and can be impacted by diet. This study determined if 2-weeks of blueberry and/or acute banana ingestion influenced generation of n-6 and n-3 PUFA-derived oxylipins during recovery from exercise-induced physiological stress. Cyclists ( = 59, 39 ± 2 years of age) were randomized to freeze-dried blueberry or placebo groups, and ingested 26 grams/d (1 cup/d blueberries equivalent) for 2 weeks.

Human GDPD3 overexpression promotes liver steatosis by increasing lysophosphatidic acid production and fatty acid uptake.

The glycerol phosphate pathway produces more than 90% of the liver triacylglycerol (TAG). LysoPA, an intermediate in this pathway, is produced by glycerol-3-phosphate acyltransferase. Glycerophosphodiester phosphodiesterase domain containing 3 (GDPD3), whose gene was recently cloned, contains lysophospholipase D activity, which produces LysoPA from lysophospholipids.

Simultaneous quantification of free fatty acids and acylcarnitines in plasma samples using dansylhydrazine labeling and liquid chromatography-triple quadrupole mass spectrometry.

Free fatty acid (FFA) and acylcarnitine (AcCar) are key elements of energy metabolism. Dysregulated levels of FFA and AcCar are associated with genetic defects and other metabolic disorders. Due to differences in the physicochemical properties of these two classes of compounds, it is challenging to quantify FFA and AcCar in human plasma using a single method.