• lipidomics
• metabolic reprogramming
• primary biliary cholangitis
• proteomics
• targeted metabolomics

• Humans
• Metabolomics/methods
• Liver/metabolism
• Liver/pathology
• Proteomics/methods
• Lipidomics/methods
• Female
• Middle Aged
• Male
• Glycolysis
• Liver Cirrhosis, Biliary/metabolism
• Liver Cirrhosis, Biliary/pathology
• Autophagy
• Fatty Acids/metabolism
• Apoptosis
• Purines/metabolism
• Carnitine/metabolism
• Carnitine/analogs & derivatives
• Bile Acids and Salts/metabolism
• Lipid Metabolism
• Aged
• Case-Control Studies
• Adult

• autoimmune disease
• biomarker and diagnosis
• metabolites
• metabolomics analysis

• Sjögren’s syndrome
• lipidomics
• plasma
• primary biliary cholangitis
• ursodeoxycholic acid

• Amphibian
• Bile acids
• Heavy metals
• Intestinal microbiota

• Humans
• Animals
• Copper/toxicity
• Lead/toxicity
• Ecosystem
• Gastrointestinal Microbiome
• Bufonidae
• Larva
• Bile Acids and Salts

• L-carnitine
• acylcarnitines
• biomarkers
• carnitines
• metabolites
• metabolomics
• ocular diseases
• ophthalmology

• Infant, Newborn
• Humans
• Ophthalmology
• Glaucoma, Open-Angle/metabolism
• Carnitine/metabolism
• Vitreous Body/metabolism
• Biomarkers/metabolism

Primary biliary cholangitis (PBC) and autoimmune hepatitis (AIH) are two unexplained immune diseases. The golden standard for diagnosis of these diseases requires a liver biopsy. Liver biopsy is not widely accepted by patients because of its invasive nature, and atypical liver histology can confuse diagnosis. In view of the lack of effective diagnostic markers for PBC and AIH, combined with the increasingly mature metabolomics technologies, including full-contour metabolomics and target.

To determine non-invasive, reliable, and sensitive biochemical markers for the differential diagnosis of PBC and AIH.

Serum samples from 54 patients with PBC, 26 patients with AIH and 30 healthy controls were analyzed by Ultra-high performance liquid chromatography-tandem mass spectrometry serum metabolomics. The metabolites and metabolic pathways were identified, and the metabolic changes, metabolic pathways and inter-group differences between PBC and AIH were analyzed. Fifteen kinds of target metabolites of bile acids (BAs) were quantitatively analyzed by SRM, and the differential metabolites related to the diagnosis of PBC were screened by receiver operating characteristic curve analysis.

We found the changes in the levels of amino acids, BAs, organic acids, phospholipids, choline, sugar, and sugar alcohols in patients with PBC and AIH. Furthermore, the SRM assay of BAs revealed the increased levels of chenodeoxycholic acid, lithocholic acid (LCA), taurolithocholic acid (TLCA), and LCA + TLCA in the PBC group compared with those in the AIH group. The levels of BAs may be used as biomarkers to differentiate PBC from AIH diseases. The levels of glycochenodeoxycholic acid, glycochenodeoxycholic sulfate, and taurodeoxycholic acid were gradually elevated with the increase of Child-Pugh class, which was correlated with the severity of disease.

The results demonstrated that the levels of BAs could serve as potential biomarkers for the early diagnosis and assessment of the severity of PBC and AIH.

• Primary biliary cholangitis
• Autoimmune hepatitis
• Biomarkers
• Serum metabolic profiling
• Bile acids
• Ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry

• Humans
• Hepatitis, Autoimmune
• Liver Cirrhosis, Biliary/metabolism
• Bile Acids and Salts
• Metabolomics/methods
• Biomarkers

• Bile acids
• Liver cirrhosis
• Metabolomics

• Bile Acids and Salts
• Biomarkers
• Humans
• Liver Cirrhosis/diagnosis
• Metabolomics
• Prospective Studies

• National Natural Science Foundation of China

• bile acids
• liver cirrhosis
• metabolomics

• Bile Acids and Salts
• Biomarkers/blood
• Cohort Studies
• Humans
• Liver Cirrhosis/diagnosis
• Meta-Analysis as Topic
• Observational Studies as Topic
• Randomized Controlled Trials as Topic
• Research Design
• Systematic Reviews as Topic

• biomarker
• cholestasis
• liver
• omics

• LASSO
• biomarkers
• clear cell renal cell carcinoma
• lipidomics
• machine learning
• mass spectrometry
• support vector machines
• ultraperformance liquid chromatography

• Bile acids
• Gut microbiota
• Primary biliary cholangitis
• Ursodeoxycholic acid

• Bile acid
• Cholestasis
• Cultured bear bile
• Metabolomics
• Transporter

• NAFL
• NASH
• alcoholic liver disease
• biomarker
• cholestasis
• cirrhosis
• fibrosis
• lipidomics
• metabolomics
• premalignant

• Bile acid
• Cholestasis
• DDC
• Huangqi decoction
• NF-κB
• Nrf2

• Animals
• Bile Acids and Salts/metabolism
• Cholestasis, Intrahepatic/chemically induced
• Cholestasis, Intrahepatic/drug therapy
• Cholestasis, Intrahepatic/metabolism
• Cholestasis, Intrahepatic/pathology
• Dicarbethoxydihydrocollidine
• Drugs, Chinese Herbal/chemistry
• Drugs, Chinese Herbal/pharmacology
• Enzymes/metabolism
• Hepatitis/drug therapy
• Hepatitis/etiology
• Liver/drug effects
• Liver/metabolism
• Liver/pathology
• Liver Cirrhosis/drug therapy
• Liver Cirrhosis/pathology
• Male
• Mice, Inbred C57BL
• NF-E2-Related Factor 2/metabolism
• NF-kappa B/antagonists & inhibitors
• NF-kappa B/metabolism
• Protective Agents/pharmacology

• PBC
• metabonome
• microbiota
• pruritus

This study aimed to analyze the differential metabolites and their metabolic pathways from the serum of patients with hepatitis B cirrhosis, with two typical patterns of Gan Dan Shi Re (GDSR) and Gan Shen Yin Xu (GSYX) based on the theory of traditional Chinese medicine (TCM). It also investigated the variation in the internal material basis for the two types of patterns and provided an objective basis for classifying TCM patterns using metabolomic techniques.

The serum samples taken from 111 qualified patients (40 GDSR cases, 41 GSYX cases, and 30 Latent Pattern (LP) cases with no obvious pattern characters) and 60 healthy volunteers were tested to identify the differential substances relevant to hepatitis B cirrhosis and the two typical TCM patterns under the gas chromatography–time-of-flight mass spectrometry platform. The relevant metabolic pathways of differential substances were analyzed using multidimensional statistical analysis.

After excluding the influence of LP groups, six common substances were found in GDSR and GSYX patterns, which were mainly involved in the metabolic pathways of glycine, serine, threonine, and phenylalanine. Eight specific metabolites involved in the metabolic pathways of linoleic, glycine, threonine, and serine existed in the two patterns.

The data points on the metabolic spectrum were found to be well distributed among the differential substances between the two typical TCM patterns of patients with hepatitis B cirrhosis using metabolomic techniques. The differential expression of these substances between GDSR and GSYX patterns provided an important objective basis for the scientific nature of TCM pattern classification at the metabolic level.

• Bile acid
• Reduced nicotinamide adenine dinucleotide
• Screen printed carbon electrode
• Serum
• Tris(bipyridine)-ruthenium (II)

Primary biliary cholangitis (PBC) is a chronic progressive cholestatic disease characterized by destruction of small- and medium-sized intrahepatic bile ducts. It is no longer a rare disease, since many new asymptomatic cases are incidentally identified. Liver biopsy is diagnostically critical but not always feasible or practical to be performed. Many potential, noninvasive, markers have been proposed to replace liver biopsy and further provide the assessment of disease severity and ultimate prognosis. In this review, we evaluated serum biomarkers proposed for diagnosis, extent of fibrosis, disease prognosis and attempts for early prediction of treatment response. Older biochemical and immunological markers are presented along with recent reports including the role of microRNAs and promising results based on proteomics and metabolomics.

• autoantibodies
• microRNAs
• primary biliary cholangitis
• proteomics
• treatment response

Bile acids (BAs) are important regulatory factors of life activities, which are involved in the regulation of glucose, lipid and energy metabolisms, and closely associated with intestinal hormones, microbiotas and energy balance. BAs abnormalities easily lead to inflammation and metabolic diseases, in turn, the progress of diseases could influence characteristics of BAs. Therefore, accurate detection of BAs contents is of great significance to disease prevention, diagnosis and treatment. At present, the most widely used enzymatic method in clinical practice is applicable to the detection of total bile acid (TBA). In laboratory research, different types of BAs can be accurately separated and quantified by liquid chromatography-mass spectrometry (LC-MS). The metabolic profiling of BAs based on detection technologies can completely and accurately monitor their types and contents, playing a crucial role in disease prevention, diagnosis and treatment. We herein reviewed the main detection technologies of BAs and the application of metabolic profiling in related diseases in recent years.

• Bile acids
• Detection technologies
• Liquid chromatography-mass spectrometry
• Metabolic disease
• Metabolic profiling

• Amino Acids/metabolism
• Animals
• Biomarkers
• Biopsy
• Computational Biology/methods
• Lipid Metabolism
• Liver Cirrhosis/etiology
• Liver Cirrhosis/metabolism
• Liver Cirrhosis/pathology
• Male
• Metabolic Networks and Pathways
• Metabolome
• Metabolomics/methods
• ROC Curve
• Rats
• Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

Radix Salviae miltiorrhizae (SM) and Lignum Dalbergiae odoriferae (DO) are traditional Chinese medicinal herbs used to treat ischemic heart disease and other cardiovascular diseases; however, to the best of our knowledge, there are currently few studies regarding their effects. The present study aimed to investigate the cardioprotective effects of SM and DO during myocardial ischemia/reperfusion (MI/R) injury in rats, and explore the molecular mechanisms that underlie their actions. In the present study, Sprague-Dawley rats were pretreated with SM, the aqueous extract of DO (DOA) and the volatile oil of DO (DOO), either as a monotherapy or in combination for 7 days. Subsequently, the rats were subjected to 30 min of ischemia followed by 180 min of reperfusion. Traditional pharmacodynamic evaluation and metabonomics based on gas chromatography/time-of-flight mass spectrometry were used to identify the therapeutic effects of these traditional Chinese medicines. The results revealed that SM, DOA and DOO monotherapies ameliorated cardiac function, and this effect was strengthened further when used in combined therapies. Among the combined treatments, SM + DOO exhibited the greatest potential (P<0.05) to improve electrocardiogram results and heart rate, reduce the heart weight index and myocardial infarct size, and decrease the levels of creatine kinase-MB and lactate dehydrogenase. In addition, metabonomics-based findings, including the principal component analysis and partial least squares discriminant analysis score plot of the metabolic state in rat serum, provided confirmation for the aforementioned results, verifying that SM + DOO exerted synergistic therapeutic efficacies to exhibit a greater effect on rats with MI/R injury when compared with the other pretreatment groups. Furthermore, the most effective duration of SM + DOO treatment was 30 min and the least effective duration was 180 min. Treatment with SM + DOO also significantly (P<0.01) reduced the number of terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling-positive cells, tumor necrosis factor-α andinterleukin-6 expression, and malondialdehyde content, and increased the serum and tissue activity of superoxide dismutase. These results indicated that the combined effects of SM + DOO may be more effective compared with the single pretreatments against MI/R injury in rats. This effect may be achieved partly through anti-apoptotic, antioxidant and anti-inflammatory activities. Therefore, SM + DOO may be considered an effective and promising novel strategy for the prophylaxis and treatment of ischemic heart disease.

Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease associated with profound metabolic changes. The purpose of this study was to identify a distinctive metabolic signature from the training set with 29 PBC patients, 30 hepatitis B virus (HBV)-caused cirrhosis (HBC) and 41 healthy controls, and to validate the applicability and stability of the distinctive model from the validation set with 21 PBC patients, 7 autoimmune hepatitis (AIH) and 9 HBC. The sera were investigated using high resolution nuclear magnetic resonance (NMR) and the datasets were analyzed pairwise using pattern recognition methods. 45 distinguishable metabolites were identified and 15 metabolic pathways were reprogrammed. The altered metabolic pathways were associated with glucose, fatty acid and amino acid metabolites. Logistic regression and ROC analysis were used to establish a diagnostic model with the equated (p) = −12.22–3.46*log(4-hydroxyproline) + 6.62*log(3-hydroxyisovalerate) − 2.44*log(citraconate) − 3.80*log(pyruvate). The area under the curve (AUC) of the optimized model was 0.937 (95% confidence interval (CI): 0.868–0.976) in the training set and 0.890 (95% CI: 0.743–0.969) in the validation set. These results not only revealed the potential pathogenesis of PBC, but also provided a feasible diagnostic tool for PBC populations through detection of serum metabolites.

Primary biliary cholangitis (PBC), formerly referred to as primary biliary cirrhosis, is an infrequent progressive intrahepatic cholestatic autoimmune illness that can evolve into hepatic fibrosis, hepatic cirrhosis, hepatic failure, and, in some cases, hepatocellular carcinoma. The disease itself is characterized by T-lymphocyte-mediated chronic non-suppurative destructive cholangitis and elevated serum levels of extremely specific anti-mitochondrial autoantibodies (AMAs). In this article, we will not only review epidemiology, risk factors, natural history, predictive scores, radiologic approaches (e.g., acoustic radiation force impulse imaging, vibration controlled transient elastography, and magnetic resonance elastography), clinical features, serological characteristics covering biochemical markers, immunoglobulins, infections markers, biomarkers, predictive fibrosis marker, specific antibodies (including AMAs such as AMA-M2), anti-nuclear autoantibodies [such as anti-multiple nuclear dot autoantibodies (anti-sp100, PML, NDP52, anti-sp140), anti-rim-like/membranous anti-nuclear autoantibodies (anti-gp210, anti-p62), anti-centromere autoantibodies, and some of the novel autoantibodies], histopathological characteristics of PBC, diagnostic advances, and anti-diastole of PBC. Furthermore, this review emphasizes the recent advances in research of PBC in terms of therapies, including ursodeoxycholic acid, budesonide, methotrexate, obeticholic acid, cyclosporine A, fibrates such as bezafibrate and fenofibrate, rituximab, mesenchymal stem cells transplant, and hepatic transplant. Currently, hepatic transplant remains the only optimal choice with acknowledged treatment efficiency for end-stage PBC patients.

• Autoimmune liver diseases
• Primary biliary cholangitis
• Primary biliary cirrhosis
• Diagnosis
• Therapy

RCC usually develops and progresses asymptomatically and, when detected, it is frequently at advanced stages and metastatic, entailing a dismal prognosis. Therefore, there is an obvious demand for new strategies enabling an earlier diagnosis. The importance of metabolic rearrangements for carcinogenesis unlocked a new approach for cancer research, catalyzing the increased use of metabolomics. The present study aimed the NMR metabolic profiling of RCC in urine samples from a cohort of RCC patients (n = 42) and controls (n = 49). The methodology entailed variable selection of the spectra in tandem with multivariate analysis and validation procedures. The retrieval of a disease signature was preceded by a systematic evaluation of the impacts of subject age, gender, BMI, and smoking habits. The impact of confounders on the urine metabolomics profile of this population is residual compared to that of RCC. A 32-metabolite/resonance signature descriptive of RCC was unveiled, successfully distinguishing RCC patients from controls in principal component analysis. This work demonstrates the value of a systematic metabolomics workflow for the identification of robust urinary metabolic biomarkers of RCC. Future studies should entail the validation of the 32-metabolite/resonance signature found for RCC in independent cohorts, as well as biological validation of the putative hypotheses advanced.

A variety of diseases are included under the umbrella term ‘cholangitis’, including hepatobiliary diseases with an autoimmune pathogenesis (such as primary sclerosing cholangitis, primary biliary cholangitis, and IgG4-associated sclerosing cholangitis) and disease processes associated with intraductal stones and infectious etiologies (such as ascending bacterial cholangitis, recurrent pyogenic cholangitis, and liver fluke-associated cholangitis). Recent advances in the pathophysiologic bases of these disorders, particularly with respect to the autoimmune variety, are allowing improved diagnosis and prognostication as well as providing the opportunity to refine and re-imagine treatment modalities. The aim of this review is to highlight selected advances in cholangitis research that point to novel insights into the pathophysiology, diagnosis, and treatment of this diverse array of disorders.

• IgG4-associated sclerosing cholangitis
• cholangitis
• cholangitis research
• primary biliary cholangitis
• primary sclerosing cholangitis