Unsaturated fatty acid profiles and prognostic significance in epilepsy patients: A comprehensive analysis using UPLC-MS/MS and SVM algorithm.

Unsaturated fatty acids (UFAs) play a crucial physiological role in human body. However, the concentration-related changes and prognostic significance of UFAs in epilepsyremain unclear. An optimized ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) approach was developed to measure six key UFAs: oleic acid (OA), linoleic acid (LA), arachidonic acid (AA), α-linolenic acid (ALA), docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA).

The metabolic profiles of endogenous and exogenous substances in a poor metabolizer of humanized CYP2D6 model.

Background: Species differences in CYP2D6 drug metabolism complicate the extrapolation of in vivo pharmacokinetic data to humans and impact the prediction of drug responses. This study aimed to develop an in vivo model to predict human responses to CYP2D6 metabolized compounds and to evaluate medication risks and disease development.

Methods: We used embryonic stem cell (ES) targeting and CRISPR-Cas9 technology to create a humanized CYP2D6 mouse model by inserting the human wild-type CYP2D6 gene and knocking out the mouse Cyp2d locus.

Diagnostic and prognostic value of diquat plasma concentration and complete blood count in patients with acute diquat poisoning based on random forest algorithms.

Currently, the incidence of diquat (DQ) poisoning is increasing, and quickly predicting the prognosis of poisoned patients is crucial for clinical treatment. In this study, a total of 84 DQ poisoning patients were included, with 38 surviving and 46 deceased. The plasma DQ concentration of DQ poisoned patients, determined by liquid chromatography-mass spectrometry (LC-MS) were collected and analyzed with their complete blood count (CBC) indicators.

Synaptotagmin-1 antagonizes paraquat intracellular accumulation and nephrocyte toxicity by up-regulating SERBP1/GLUT2 expression.

Acute kidney injury (AKI) is common and an independent risk factor for mortality in patients with paraquat (PQ) poisoning. Currently, no specific antidote is available. Synaptotagmin-1 (SYT1) has been identified as a key protein that facilitates PQ efflux in PQ-resistant A549 cells, thereby preventing PQ-induced lung injury.

Abnormalities of serum lipid metabolism in patients with acute paraquat poisoning caused by ferroptosis.

As the mechanism of paraquat (PQ) poisoning is still not fully elucidated, and no specific treatment has been developed in medical practice, the management of PQ poisoning continues to present a medical challenge. In this study, the objective was to investigate the early metabolic changes in serum metabolism and identify the key metabolic pathways involved in patients with PQ poisoning. Quantitative analysis was conducted to determine the relevant metabolites.

A novel mechanism of Dimethyl ester of Alpha-ketoglutarate in suppressing Paraquat-induced BEAS-2B cell injury by alleviating GSDME dependent pyroptosis.

Background: Acute lung injury (ALI) induced by paraquat (PQ) progresses rapidly, leading to high mortality; however, there is no specific antidote. Our limited knowledge of the pathogenic toxicological mechanisms of PQ has hindered the development of treatments against PQ exposure.

Purpose: Pyroptosis is a form of programmed cell death recently identified as a novel molecular mechanism adopted by chemotherapeutic drugs for cancer therapy.

A double-blind, randomized, placebo-controlled, single-center clinical trial of jiaotaiwan for the treatment of insomnia symptoms caused by disharmony of the heart and kidney.

Jiaotaiwan (JTW) is a classical tranquillizing prescription in traditional Chinese medicine (TCM) for the treatment of insomnia symptoms caused by disharmony of the heart and kidney (ISDHK). This study aimed to evaluate the effectiveness and safety of JTW for treating ISDHK in a double-blind, randomized, placebo-controlled trial. From September 2018 to February 2020, 128 participants with ISDHK were included in this single-center clinical trial.

Marked Efficiency Improvement of FAPbSnBr Perovskite Light-Emitting Diodes by Optimization of the Light-Emitting Layer and Hole-Transport Layer.

Highly luminescent FAPbSnBr nanocrystals with an average photoluminescence (PL) quantum yield of 92% were synthesized by the ligand-assisted reprecipitation method. The 41-nm-thick perovskite film with a smooth surface and strong PL intensity was proven to be a suitable luminescent layer for perovskite light-emitting diodes (PeLEDs). Electrical tests indicate that the double hole-transport layers (HTLs) played an important role in improving the electrical-to-optical conversion efficiency of PeLEDs due to their cascade-like level alignment.

Vesicle transport related protein Synaptotagmin-1 mediates paraquat transport to antagonize paraquat toxicity.

In this study, A549/PQ cells with moderate resistance to paraquat (PQ) were obtained by treating A549 cells with PQ, their growth rate was slowed down, the accumulation concentration of PQ and the levels of growth inhibition, injury and early apoptosis induced by PQ were significantly lower than those of parental A549 cells. Microarray screening and RT-qPCR detection found that Synaptotagmin-1 (SYT1) expression in drug-resistant cells was significantly increased, and PQ further enhanced its expression. After inhibiting SYT1 expression in A549/PQ cells, cell viability, intracellular PQ concentration and the expression of Bcl-2, SNAP25 and RAB26 were significantly reduced, while the mortality, early apoptosis rate and Bax expression were significantly increased.

Controlling CRISPR-Cas9 by guide RNA engineering.

The clustered regularly interspaced short palindromic repeats (CRISPR) system is a product of million years of evolution by microbes to fight against invading genetic materials. Around 10 years ago, scientists started to repurpose the CRISPR as genetic tools by molecular engineering approaches. The guide RNA provides a versatile and unique platform for the innovation to improve and expand the application of CRISPR-Cas9 system.

Jiaotaiwan increased GABA level in brain and serum, improved sleep via increasing NREM sleep and REM sleep, and its component identification.

Ethnopharmacological Relevance: Jiaotaiwan (JTW) is good at communicating the heart and kidney. That meets the main mechanism of insomnia in traditional Chinese medicine. But the mechanism of JTW in promoting sleep is not clear.

Plasma Concentration After the First Hemoperfusion has a High Predictive Value in Medium Level Acute Paraquat-Poisoned Patients.

Background: Paraquat ( PQ) is very poisonous to humans and animals and there is no effective clinical antidote . The efficacy of hemoperfusion (HP) treatment for PQ poisoning remains controversial. To explore new ways to predict the prognosis of patients with acute PQ poisoning and assist in the development of better hemopurification treatment strategies.

UPLC-MS/MS Determination of Linezolid and Heme in Plasma of Infected Patients and Correlation Analysis.

Linezolid can cause serious haematological toxicity, such as thrombocytopenia and aneamia. Heme, composed of iron and porphyrin, is an important component of hemoglobin. In order to investigate the relationship between the concentration of linezolid and heme in the plasma of infected patients, a UPLC-MS/MS method that can determine the concentrations of linezolid and heme simultaneously was developed and validated.

Effects of long-term alcohol exposure on the pharmacokinetic profiles of ketamine and norketamine in rats.

Background: Alcohol abuse has become a serious health issue worldwide. Ketamine can reduce addiction risk among patients with alcohol use disorders. This study aimed to determine the effects of alcohol on the pharmacokinetics of ketamine during long-term alcohol exposure.

Jiao-tai-wan for insomnia symptoms caused by the disharmony of the heart and kidney: a study protocol for a randomized, double-blind, placebo-controlled trial.

Background: Insomnia seriously affects people's normal lives and work. However, effective treatment strategies are scarce. The purpose of this study is to explore the efficacy and safety of Jiao-tai-wan (JTW) for ameliorating insomnia symptoms caused by disharmony of the heart and kidney.

Simultaneous determination of five essential amino acids in plasma of Hyperlipidemic subjects by UPLC-MS/MS.

Background: Millions of adults have been reported with hyperlipemia in the world. It is still unclear whether the plasma level of essential amino acids (AAs) will be influenced by the hyperlipemia. This study was aimed to investigate the AAs levels and the underlying metabolic relationship in hyperlipidemic subjects.

Determination of four omega-3 polyunsaturated fatty acids by UPLC-MS/MS in plasma of hyperlipidemic and normolipidemic subjects.

Background: Omega-3 polyunsaturated fatty acids (PUFAs), including alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and docosapentaenoic acid (DPA), play critical roles in numerous biochemical reactions. Our aim is to develop a rapid and sensitive method for simultaneous determination of ALA, EPA, DHA and DPA in the plasma of hyperlipidemic and normolipidemic subjects.

Methods: An ultra-high-performance liquid chromatography-tandem mass spectrometric (UPLC-MS/MS) method of ALA, EPA, DHA, and DPA was developed with chlorzoxazone as the internal standard (IS).

Metabolomics Analysis in Acute Paraquat Poisoning Patients Based on UPLC-Q-TOF-MS and Machine Learning Approach.

Most paraquat (PQ) poisoned patients died from acute multiple organ failure (MOF) such as lung, kidney, and heart. However, the exact mechanism of intoxication is still unclear. In order to find out the initial toxic mechanism of PQ poisoning, a blood metabolomics study based on ultraperformance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) and efficient machine learning approach was performed on 23 PQ poisoned patients and 29 healthy subjects.

A microRNA-inducible CRISPR-Cas9 platform serves as a microRNA sensor and cell-type-specific genome regulation tool.

microRNAs (miRNAs) are small noncoding RNAs that play important regulatory roles in plants, animals and viruses. Measuring miRNA activity in vivo remains a big challenge. Here, using an miRNA-mediated single guide RNA (sgRNA)-releasing strategy and dCas9-VPR to drive a transgene red fluorescent protein, we create an miRNA sensor that can faithfully measure miRNA activity at cellular levels and use it to monitor differentiation status of stem cells.

Simvastatin prevents and ameliorates depressive behaviors via neuroinflammatory regulation in mice.

Background: Statins play a beneficial role in the treatment of coronary artery disease and are widely prescribed to prevent hypercholesterolemia. Previous studies have demonstrated that statins also have anti-inflammatory and immunomodulatory properties, and these are being explored for potential benefits in depression. However, the role of statins in the treatment of depression has not been well examined.

Nrf2 overexpression protects against paraquat-induced A549 cell injury primarily by upregulating P-glycoprotein and reducing intracellular paraquat accumulation.

Paraquat (PQ) intoxication causes thousands of mortalities every year, worldwide. Its pulmonary-targeted accumulation and the acute lung injury it subsequently causes, remain a challenge for detoxification treatment. A previous study has demonstrated that the upregulation of nuclear factor erythroid-2 related factor 2 (Nrf2) prevents PQ toxicity in cell line and murine models.

Chaos enhanced grey wolf optimization wrapped ELM for diagnosis of paraquat-poisoned patients.

Paraquat (PQ) poisoning seriously harms the health of humanity. An effective diagnostic method for paraquat poisoned patients is a crucial concern. Nevertheless, it's difficult to identify the patients with low intake of PQ or delayed treatment.

Linezolid Inhibited Synthesis of ATP in Mitochondria: Based on GC-MS Metabolomics and HPLC Method.

Linezolid has been widely used in serious infections for its effective inhibiting effect against multidrug-resistant gram-positive pathogens. However, linezolid caused severe adverse reactions, such as thrombocytopenia, anaemia, optic neuropathy, and near-fatal serotonin syndrome. In order to investigate the toxicity of linezolid, twenty-four Sprague-Dawley rats were randomly divided into: control group (n=7), low-group (n=8), and high-group (n=9).

Metabolism of liver CYP450 and ultrastructural changes after long-term administration of aspirin and ibuprofen.

Worldwide, aspirin and ibuprofen are the most commonly used non-steroidal anti-inflammatory drugs (NSAIDs). Some adverse reactions, including gastrointestinal reactions, have been concerned extensively. Nevertheless, the mechanism of liver injury remains unclear.