Metabolomics reveals that sulfotransferase 1 may regulate colchicine-induced liver injury.

Colchicine is widely used to treat gouty arthritis for years. Previous studies showed that colchicine overdose can cause liver damage, yet the mechanism underlying its hepatotoxicity remains unclear. In this study, hepatotoxicity of colchicine was investigated in vivo.

Comprehensive biomarker analysis of metabolomics in different syndromes in traditional Chinese medical for prediabetes mellitus.

Background: Prediabetes mellitus (PreDM) is a high-risk state for developing type 2 diabetes mellitus (T2DM) and often goes undiagnosed, which is closely associated with obesity and characterized by insulin resistance that urgently needs to be treated.

Purpose: To obtain a better understanding of the biological processes associated with both "spleen-dampness" syndrome individuals and those with dysglycaemic control at its earliest stages, we performed a detailed metabolomic analysis of individuals with various early impairments in glycaemic control, the results can facilitate clinicians' decision making and benefit individuals at risk.

Methods: According to the diagnostic criteria of TCM patterns and PreDM, patients were divided into 4 groups with 20 cases, patients with syndrome of spleen deficiency with dampness encumbrance and PreDM (PDMPXSK group), patients with syndrome of dampness-heat in the spleen and PreDM (PDMSRYP group), patients with syndrome of spleen deficiency with dampness encumbrance and normal blood glucose (NDMPXSK group), and patients with syndrome of dampness-heat in the spleen and normal blood glucose (NDMSRYP group).

Utilising a Clinical Metabolomics LC-MS Study to Determine the Integrity of Biological Samples for Statistical Modelling after Long Term -80 °C Storage: A TOFI_Asia Sub-Study.

Biological samples of lipids and metabolites degrade after extensive years in -80 °C storage. We aimed to determine if associated multivariate models are also impacted. Prior TOFI_Asia metabolomics studies from our laboratory established multivariate models of metabolic risks associated with ethnic diversity.

Integrating network pharmacology and drug side-effect data to explore mechanism of liver injury-induced by tyrosine kinase inhibitors.

Tyrosine kinase inhibitors (TKIs) are highly efficient small-molecule anticancer drugs. Despite the specificity and efficacy of TKIs, they can produce off-target effects, leading to severe liver toxicity, and even some of them are labeled as black box hepatotoxicity. Thus, we focused on representative TKIs associated with severe hepatic adverse events, namely lapatinib, pazopanib, regorafenib, and sunitinib as objections of study, then integrated drug side-effect data from United State Food and Drug Administration (U.

Engineered mesenchymal stem cell-derived extracellular vesicles constitute a versatile platform for targeted drug delivery.

Extracellular vesicles (EVs) are promising therapeutic carriers owing to their ideal size range and intrinsic biocompatibility. However, limited targeting ability has caused major setbacks in the clinical application of EV therapeutics. To overcome this, we genetically engineered natural free streptavidin (SA) on the cellular surface of bone marrow mesenchymal stem cells (BMSCs) and obtained typical EVs from these cells (BMSC-EVs).

Celastrol as an intestinal FXR inhibitor triggers tripolide-induced intestinal bleeding: Underlying mechanism of gastrointestinal injury induced by Tripterygium wilfordii.

Background: Tripterygium wilfordii has been widely used for the treatment of rheumatoid arthritis, which is frequently accompanied by severe gastrointestinal damage. The molecular mechanism underlying the gastrointestinal injury of Tripterygium wilfordii are yet to be elucidated.

Methods: Transmission electron microscopy, and pathological and biochemical analyses were applied to assess intestinal bleeding.

Metabolomics Reveals Gut Microbiota Contribute to PPARα Deficiency-Induced Alcoholic Liver Injury.

Incidence and mortality rates of alcoholic liver disease (ALD) is one of the highest in the world. In the present study, we found that the genetic knockout nuclear receptor the peroxisome proliferator-activated receptor α (PPARα) exacerbated ALD. Lipidomics of the liver revealed changed levels of lipid species encompassing phospholipids, ceramides (CM), and long-chain fatty acids in -null mice induced by ethanol.

The impact of ethnicity and intra-pancreatic fat on the postprandial metabolome response to whey protein in overweight Asian Chinese and European Caucasian women with prediabetes.

The "Thin on the Outside Fat on the Inside" TOFI_Asia study found Asian Chinese to be more susceptible to Type 2 Diabetes (T2D) compared to European Caucasians matched for gender and body mass index (BMI). This was influenced by degree of visceral adipose deposition and ectopic fat accumulation in key organs, including liver and pancreas, leading to altered fasting plasma glucose, insulin resistance, and differences in plasma lipid and metabolite profiles. It remains unclear how intra-pancreatic fat deposition (IPFD) impacts TOFI phenotype-related T2D risk factors associated with Asian Chinese.

Comparative metabolism of THCA and THCV using UHPLC-Q-Exactive Orbitrap-MS.

Delta(9)-tetrahydrocannabinolic acid (THCA) and delta(9)-tetrahydrocannabivarin (THCV) are phytocannabinoids with a similar structure derived from and possess a variety of biological activities. However, the relationship between the metabolic characterisation and bioactivity of THCA and THCV remains elusive.To explore the relationship between the metabolism of THCA and THCV and their underlying mechanism of activity, human/mouse liver microsomes and mouse primary hepatocytes were used to compare the metabolic maps between THCA and THCV through comparative metabolomics.

Tripterygium wilfordii protects against an animal model of autoimmune hepatitis.

Ethnopharmacological Relevance: Tripterygium wilfordii tablets (TWT) is widely used to treat autoimmune diseases such as rheumatoid arthritis. Celastrol, one main active ingredient in TWT, has been shown to produce a variety of beneficial effects, including anti-inflammatory, anti-obesity, anti-cancer, and immunomodulatory. However, whether TWT could protect against Concanavalin A (Con A)-induced hepatitis remains unclear.

Comparative Metabolomic Profiling of the Metabolic Differences of Δ9-Tetrahydrocannabinol and Cannabidiol.

More than one hundred cannabinoids have been found in cannabis. Δ9-Tetrahydrocannabinol (THC) is the recognized addictive constituent in cannabis; however, the mechanisms underlying THC-induced toxicity remain elusive. To better understand cannabis-induced toxicity, the present study compared the metabolic pathways of THC and its isomer cannabidiol (CBD) in human and mouse liver microsomes using the metabolomic approach.

Recent advances in metabolism and toxicity of tyrosine kinase inhibitors.

Small molecule tyrosine kinase inhibitors (TKIs) are widely used as anticancer drugs approved by U.S. FDA.

Dissecting the relationship between plasma and tissue metabolome in a cohort of women with obesity: Analysis of subcutaneous and visceral adipose, muscle, and liver.

Untargeted metabolomics of blood samples has become widely applied to study metabolic alterations underpinning disease and to identify biomarkers. However, understanding the relevance of a blood metabolite marker can be challenging if it is unknown whether it reflects the concentration in relevant tissues. To explore this field, metabolomic and lipidomic profiles of plasma, four sites of adipose tissues (ATs) from peripheral or central depot, two sites of muscle tissue, and liver tissue from a group of nondiabetic women with obesity who were scheduled to undergo bariatric surgery (n = 21) or other upper GI surgery (n = 5), were measured by liquid chromatography coupled with mass spectrometry.

Untargeted metabolomics reveals plasma metabolites predictive of ectopic fat in pancreas and liver as assessed by magnetic resonance imaging: the TOFI_Asia study.

Background: Excess visceral obesity and ectopic organ fat is associated with increased risk of cardiometabolic disease. However, circulating markers for early detection of ectopic fat, particularly pancreas and liver, are lacking.

Methods: Lipid storage in pancreas, liver, abdominal subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) from 68 healthy or pre-diabetic Caucasian and Chinese women enroled in the TOFI_Asia study was assessed by magnetic resonance imaging/spectroscopy (MRI/S).

Metabolomic signatures for visceral adiposity and dysglycaemia in Asian Chinese and Caucasian European adults: the cross-sectional TOFI_Asia study.

Background: Asian Chinese are more susceptible to deposition of visceral adipose tissue (VAT) and type 2 diabetes (T2D) development than European Caucasians when matched for gender, age and body mass index (BMI). Our aims were: (i) characterise the ethnicity-specific metabolomic signature of visceral adiposity measured by dual energy X-ray absorptiometry (DXA) and fasting plasma glucose (FPG), and (ii) identify individuals susceptible to worse metabolic health outcomes.

Methods: Fasting plasma samples from normoglycaemic (n = 274) and prediabetic (n = 83) participants were analysed with liquid chromatography-mass spectrometry using untargeted metabolomics.

Tissue-Specific Sample Dilution: An Important Parameter to Optimise Prior to Untargeted LC-MS Metabolomics.

When developing a sample preparation protocol for LC-MS untargeted metabolomics of a new sample matrix unfamiliar to the laboratory, selection of a suitable injection concentration is rarely described. Here we developed a simple workflow to address this issue prior to untargeted LC-MS metabolomics using pig adipose tissue and liver tissue. Bi-phasic extraction was performed to enable simultaneous optimisation of parameters for analysis of both lipids and polar extracts.