Exploring the biomarkers and therapeutic mechanism of kidney-yang deficiency syndrome treated by You-gui pill using systems pharmacology and serum metabonomics

In this study, systems pharmacology was used to predict the molecular targets of You-gui pill (YGP) and explore the therapeutic mechanism of Kidney-Yang Deficiency Syndrome (KYDS) treated with YGP. On the basis of this, serum samples from control group, KYDS model group and YGP group rats were studied using ¹H NMR to verify the results of systems pharmacology from the level of metabonomics. Simultaneously, ¹H NMR spectra of serum samples were obtained and statistically assessed using pattern recognition analysis. Biochemical analyses of serums were performed via radioimmunoassays. Furthermore, histopathological studies were conducted on the pituitary, adrenal, and thyroid glands, and testicles of the control, KYDS and YGP rats. Using systems pharmacology to analyze the active components of YGP, 61 active compounds were finally found. These compounds were likely to have an effect on 3177 target proteins and involve 234 pathways. Using metabonomics to analyze serum from KYDS rats treated with YGP, 22 endogenous biomarkers were found. These biomarkers were mainly involved in 10 metabolic pathways. Combining systems pharmacology and metabonomics, we found that the regulation of KYDS was primarily associated with 19 active compounds of 5 Chinese herbal medicines in YGP. These active compounds mainly had an effect on 8 target proteins, including phosphoenolpyruvate carboxykinase, betaine-homocysteine s-methyltransferase 1, alcohol dehydrogenase 1C, etc. These target proteins were primarily involved in 6 overlapping pathways, namely aminoacyl-tRNA biosynthesis, glycolysis/gluconeogenesis, glycine, serine and threonine metabolism, valine, leucine and isoleucine biosynthesis, arginine and proline metabolism, and pyruvate metabolism. In addition, there were 4 non-overlapping pathways, respectively alanine, aspartate and glutamate metabolism, d-glutamine and d-glutamate metabolism, ubiquinone and other terpenoid-quinone biosynthesis, and galactose metabolism. In summary, the therapeutic effects of YGP on KYDS were mainly associated with neuroendocrine regulation, energy metabolism, amino acid metabolism, inflammatory responses, apoptosis, oxidative stress and intestinal flora metabolism. What''s more, we also found that YGP possessed the potential to protect liver and kidney function. Our study demonstrated that systems pharmacology and metabonomics methods were novel strategies for the exploration of the mechanisms of KYDS and TCM formulas.

In this study, systems pharmacology was used to predict the molecular targets of You-gui pills (YGP) and explore the therapeutic mechanism of Kidney-Yang Deficiency Syndrome (KYDS) treated with YGP.     

Deciphering metabonomics biomarkers-targets interactions for psoriasis vulgaris by network pharmacology

Objectives: Psoriasis vulgaris is a chronic inflammatory and immune-mediated skin disease. 44 metabonomics biomarkers were identified by high-throughput liquid chromatography coupled to mass spectrometry in our previous work, but the roles of metabonomics biomarkers in the pathogenesis of psoriasis is unclear.

Methods: The metabonomics biomarker-enzyme network was constructed. The key metabonomics biomarkers and enzymes were screened out by network analysis. The binding affinity between each metabonomics biomarker and target was calculated by molecular docking. A binding energy-weighted polypharmacological index was introduced to evaluate the importance of target-related pathways.

Results: Long-chain fatty acids, phospholipids, Estradiol and NADH were the most important metabonomics biomarkers. Most key enzymes belonged hydrolase, thioesterase and acyltransferase. Six proteins (TNF-alpha, MAPK3, iNOS, eNOS, COX2 and mTOR) were extensively involved in inflammatory reaction, immune response and cell proliferation, and might be drug targets for psoriasis. PI3K-Akt signaling pathway and five other pathways had close correlation with the pathogenesis of psoriasis and could deserve further research.

Conclusions: The inflammatory reaction, immune response and cell proliferation are mainly involved in psoriasis. Network pharmacology provide a new insight into the relationships between metabonomics biomarkers and the pathogenesis of psoriasis.

• KEY MESSAGES

• ??Network pharmacology was adopted to identify key metabonomics biomarkers and enzymes.

• ??Six proteins were screened out as important drug targets for psoriasis.

• ??A binding energy-weighted polypharmacological index was introduced to evaluate the importance of target-related pathways.

     

Clinical verification of a novel urinary microRNA panal: 133b, -342 and -30 as biomarkers for diabetic nephropathy identified by bioinformatics analysis

BackgroundBecause microvascular disease is one of the major drivers of diabetic complications, early detection of diabetic nephropathy (DN) by assessing the expression of exosomal microRNAs (miRNAs) in DN patients and healthy controls, may be of clinical value. The aim of this study wasto identify a novel miRNA panel of DN by combining bioinformatics analysis of miRNA databases and clinical verification to evaluate the significance of this panel as urine biomarkers for type 2 diabetic nephropathy (T2DN).Patients and MethodsPublic miRNA databases e.g miro-Ontology and miRWalk were analyzed and a novel panel of 3 microRNAs was retrieved. Meanwhile, combinatorial target prediction algorithms were applied. Multiple case-matched normal were examined by quantative RT-PCR for differential expression in urine exosomes from 210 participants, and the three identified miRNAs were validated as DN biomarkers.ResultsWe found urinary exosomalmiR-133b, miR-342, and miR-30a were expressed at significantly elevated levels in T2DN patients (P < 0.001) compared to normal. Furthermore, high-level expression of the 3 miRNAs was associated withHbA1c,systolic-diastolic blood pressure, LDL, serum creatinine, urinary albumin creatinine ratio and estimated glomerular filtration rate(eGFR). Moreover, 39.3%, 19.6% and 17.9% of patients with normo-albuminuria had positive (miR-133b, miR-342 and miR-30a, respectively); indicating the possibility of molecular changes in these patients before onset of albuminuria.ConclusionWe have identified novel urinary exosomal miRNA biomarkers of DN which were altered not only in micro and macroalbuminuric groups but also in some normoalbuminuria cases prior to albuminuria.     

Network pharmacology combined with functional metabolomics discover bile acid metabolism as a promising target for mirabilite against colorectal cancer

In this study, a combination of network pharmacology and metabolomics was used to explore the mechanism by which mirabilite regulates bile acid metabolism in the treatment of colorectal cancer. The PharmMapper web server was applied to make preliminary predictions for the treatment targets of mirabilite and to predict the interaction between mirabilite and disease targets using Discovery Studio 2.5. Furthermore, the urine metabolic profile was analyzed by the UPLC-Q-TOF-MS technology. The original data were processed by Progenesis QI software and analyzed by multivariate pattern recognition, which allowed us to reveal the metabolic disturbance in colorectal cancer and explain the therapeutic effect of mirabilite. The network pharmacology results showed that mirabilite can act on the disease targets, and the sites of action include amino acid residues Arg-364 and Asp-533, as well as nucleotides TPC-11, DG-112 and DA-113. Based on metabolomics, potential biomarkers were found to lie in the relevant pathways of bile acid metabolism, such as taurine, chenodeoxycholic acid, cholic acid, and deoxycholic acid. The results showed that mirabilite could regulate the distribution of overall metabolic disturbance, and bile acid metabolism was the main targeted pathway. Additionally, we predicted the upstream targets by ingenuity pathway analysis and found that mirabilite played a significant role in regulating the bile acid-related biomarkers, which allowed comprehensive analysis of the effect of mirabilite on colorectal cancer. This study fully explained the role of mirabilite in inhibiting colorectal cancer, which mainly occurs through bile acid metabolism, via the approach of network pharmacology combined with functional metabolomics.

In this study, a combination of network pharmacology and metabolomics was used to explore the mechanism by which mirabilite regulates bile acid metabolism in the treatment of colorectal cancer.     

Effects of Bailing capsule on diabetic nephropathy based on UPLC-MS urine metabolomics

Diabetic nephropathy (DN) is one of the most common microvascular diabetes complications and has become a threat to human health. Bailing capsules (BLCs), containing fermentation products of Cordyceps sinensis, have been commonly used for treatment of renal dysfunction, such as DN. However, mechanisms underlying the protective effects of BLC remain largely obscure and await more investigation. In this study, UPLC-MS-based comprehensive metabolomics along with pattern recognition was applied to explore the urine metabolic alteration of DN as well as therapeutic mechanisms of BLC. Nineteen differentially expressed endogenous metabolites were identified related to DN, which were involved in the perturbations of tyrosine metabolism, tryptophan metabolism, glycine metabolism, purine metabolism, glutamine metabolism, phenylalanine metabolism, histidine metabolism and TCA cycle metabolism pathways. After drug intervention, most of the biomarkers exhibited a certain extent towards normal levels (P < 0.05), which indicated that BLC was an effective drug for treating DN and might play its therapeutic role by retrieving abnormal metabolism pathways. The data obtained in this research may pave the way for further exploration of DN and provide key clues to understand the protective effect of BLC.

UPLC-MS-based metabolomics along with pattern recognition was applied to explore the metabolic alteration of diabetic nephropathy and therapeutic mechanisms of Bailing capsule.     

Functional metabolomics discover pentose and glucuronate interconversion pathways as promising targets for Yang Huang syndrome treatment with Yinchenhao Tang

Yinchenhao Tang (YCHT), a classic traditional Chinese medicine (TCM) formulae, plays an important role in the treatment of Yang Huang syndrome (YHS). With the emergence of new biomarkers of YHS uncovered via metabonomics, the underlying functional mechanisms are still not clear. Functional metabolomics aims at converting biomarkers derived from metabonomics into disease mechanisms. Here, an integrated non-target metabolomics and IPA strategy were used to investigate the YCHT intervention on YHS. Our metabolomics study has shown that the potential protective effect of YCHT on YHS mice leads to significant changes in the metabolic profile by modulating the biomarkers and regulating the metabolic disorders. Twenty two differential metabolite biomarkers and fifteen involved metabolic pathways were correlated with the regulation of YCHT treatment on YHS. Functional metabolomics identified a core biomarker, d-glucuronic acid in pentose and glucuronate interconversion pathways, which was directly related to the target prediction of UDP-glucuronosyltransferase 1A1 and eventually leaded to a series of disturbances. In conclusion, this study shows that functional metabolomics can discover metabolic pathways as promising targets.

Yinchenhao Tang (YCHT), a classic traditional Chinese medicine (TCM) formulae, plays an important role in the treatment of Yang Huang syndrome (YHS).     

Identification of independent risk factors for diabetic neuropathy progression in patients with type 2 diabetes mellitus

ObjectiveTo identify independent risk factors for diabetic neuropathy (DN) in patients with type 2 diabetes mellitus (T2DM).MethodsWe retrospectively analyzed 376 patients with T2DM at the First Affiliated Hospital of Fujian Medical University, China between January 2013 and October 2016. Multivariate logistic regression was used to explore potential risk factors for progression of DN in patients with T2DM. Effect sizes were estimated using odds ratios (ORs) and 95% confidence intervals (CIs).ResultsThe prevalence of DN in patients with T2DM was 43.1%. Multivariate logistic regression indicated that retinopathy (OR: 2.755, 95% CI: 1.599–4.746); diabetic nephropathy (OR: 2.196, 95% CI: 1.279–3.772); longer duration of T2DM (OR: 1.081, 95% CI: 1.045–1.120); use of insulin (OR: 1.091, 95% CI: 1.018–1.170); longer history of alcohol consumption (OR: 1.034, 95% CI: 1.010–1.059); and higher blood urea nitrogen (OR: 1.081, 95% CI: 1.009–1.159) were associated with increased risk of DN in patients with T2DM.ConclusionsRetinopathy, diabetic nephropathy, longer duration of T2DM, use of insulin, longer history of alcohol consumption, and higher blood urea nitrogen were independent risk factors for DN. These findings should be verified in large-scale prospective studies.     

Ultra-performance liquid chromatography-mass spectrometry-based metabolomics reveals Huangqiliuyi decoction attenuates abnormal metabolism as a novel therapeutic opportunity for type 2 diabetes

Background: As a typical chronic metabolic disease, type 2 diabetes mellitus causes a heavy health-care burden to society. In this study, we applied the metabolomics strategy to explore the potential molecular mechanism of the Huangqiliuyi decoction (HQLYD) for type-2 diabetes (T2D). Ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) combined with pattern recognition methods was utilized to select specific metabolites closely associated with HQLYD. Biomarker pathway analysis and biological network were utilized to uncover the therapeutic effect and action mechanism related to HQLYD. A total of twenty-five biomarkers were identified in the animal model, in which sixteen biomarkers are associated with HQLYD treatment for T2D. They attenuated the abnormalities of metabolic pathways such as phenylalanine, tyrosine and tryptophan biosynthesis, phenylalanine metabolism, and the citrate cycle. HQLYD also significantly elevated the serum FINS and SOD, GSP-x level in the liver and kidney, and reduced the serum TC, TG, HDL, LDL, urea, Scr, AST, ALT, FBG, IRS, MDA, and CAT level. We found that the therapeutic mechanism of HQLYD against T2D affected amino acid metabolism, glucose metabolism and lipid metabolism. Metabolomics revealed that the Huangqiliuyi decoction attenuates abnormal metabolism as a novel therapeutic opportunity for type 2 diabetes.

Background: As a typical chronic metabolic disease, type 2 diabetes mellitus causes a heavy health-care burden to society.     

Associations of serum amyloid A and 25‐hydroxyvitamin D with diabetic nephropathy: A cross‐sectional study

BackgroundThe present study investigated the relationships between serum amyloid A (SAA), 25‐hydroxyvitamin D (25(OH)VD) and diabetic nephropathy (DN) to provide evidence for the prevention and management of DN.MethodsA total of 182 patients with type 2 diabetes mellitus (T2DM) were enrolled in this study. The levels of SAA, 25(OH)VD, and other conventional indicators were measured and analyzed. Receiver operating characteristic curve analysis was applied for the combined measurement of SAA and 25(OH)VD, and risk factors for DN were evaluated using binary logistic regression analysis.ResultsThe levels of SAA in T2DM patients were significantly higher than those in healthy subjects, and the level significantly increased with the progression of DN (p < 0.05). In contrast, the level of 25(OH)VD in T2DM patients was significantly lower than that in healthy subjects, and the level significantly decreased with the progression of DN (p < 0.05). The combined measurement of SAA and 25(OH)VD distinguished DN patients from T2DM patients better than the measurement of SAA or 25(OH)VD alone. SAA was an independent risk factor for DN, and 25(OH)VD was an independent protective factor for DN.ConclusionSAA and 25(OH)VD might be used as potential markers to identify patients at increased risk of developing DN.     

Metabolomic estimation of the diagnosis of hepatocellular carcinoma based on ultrahigh performance liquid chromatography coupled with time-of-flight mass spectrometry

Metabolomics has been shown to be an effective tool for biomarker screening and pathway characterization and disease diagnosis. Metabolic characteristics of hepatocellular carcinoma (HCC) may enable the discovery of novel biomarkers for its diagnosis. In this work, metabolomics was used to investigate metabolic alterations of HCC patients. Plasma samples from HCC patients and age-matched healthy controls were investigated using high resolution ultrahigh performance liquid chromatography-mass spectrometry and metabolic differences were analyzed using pattern recognition methods. 23 distinguishable metabolites were identified. The altered metabolic pathways were associated with arginine and proline metabolism, glycine, serine and threonine metabolism, steroid hormone biosynthesis, starch and sucrose metabolism, etc. To demonstrate the utility of plasma biomarkers for the diagnosis of HCC, five metabolites comprising deoxycholic acid 3-glucuronide, 6-hydroxymelatonin glucuronide, 4-methoxycinnamic acid, 11b-hydroxyprogesterone and 4-hydroxyretinoic acid were selected as candidate biomarkers. These metabolites that contributed to the combined model could significantly increase the diagnostic performance of HCC. It has proved to be a powerful tool in the discovery of new biomarkers for disease detection and suggest that panels of metabolites may be valuable to translate our findings to clinically useful diagnostic tests.

Metabolomics has been shown to be an effective tool for biomarker screening and pathway characterization and disease diagnosis.     

Ultra-performance liquid chromatography/mass spectrometry technology and high-throughput metabolomics for deciphering the preventive mechanism of mirabilite on colorectal cancer via the modulation of complex metabolic networks

Colorectal cancer (CRC) is a highly virulent and malignant disease and always accompanied by metabolic disorders. Currently, there are no effective therapeutic drugs for the treatment of CRC. High-throughput metabolomics approaches have been used to unveil the metabolic pathways related to several diseases. In this study, ultra-performance liquid chromatography/mass spectrometry-based high-throughput metabolomics was used for deciphering the potential preventive mechanism of mirabilite on CRC via the modulation of the associated metabolic disorders; a total of 28 differential biomarkers, including indole acetaldehyde, 5-hydroxyindoleacetic acid, hypoxanthine, retinal, retinal ester, linoleic acid, stearic acid, 6-deoxocastasterone, 2-hydroxybutyric acid and LysoPC, were identified in the APC^min/+ mice. These differential biomarkers are involved in the tryptophan metabolism, glycerophospholipid metabolism and biosynthesis of unsaturated fatty acids. Note that these biomarkers and their disturbed metabolic pathways were also regulated by mirabilite. It has been found that the prevention of CRC by mirabilite is mainly associated with tryptophan metabolism; this study shows that high-throughput metabolomics can reveal the perturbed metabolic disorders targeted in the action mechanism of drug treatment.

Colorectal cancer (CRC) is a highly virulent and malignant disease and always accompanied by metabolic disorders.     

Obstructive Sleep Apnea and Diabetic Nephropathy: A cohort study

OBJECTIVE

Diabetic nephropathy (DN) is a leading cause of end-stage renal disease (ESRD). Obstructive sleep apnea (OSA) is common in type 2 diabetes and increases oxidative stress. Hence, OSA could promote the development and progression of DN.

RESEARCH DESIGN AND METHODS

This was a cohort study in adults with type 2 diabetes. Patients with known OSA or ESRD were excluded. DN was defined as the presence of albuminuria or an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m². DN progression was based on eGFR measurements. OSA was defined as apnea hypopnea index (AHI) ≥5 events/h. Serum nitrotyrosine abundance (a marker of nitrosative stress) was measured by ELISA.

RESULTS

A total of 224 patients were included. OSA and DN prevalence was 64.3 and 40.2, respectively. DN prevalence was higher in patients with OSA (OSA⁺) compared with those without OSA (OSA⁻) (49.3% vs. 23.8%, P < 0.001). After adjustment, OSA (odds ratio 2.64 [95% CI 1.13–6.16], P = 0.02) remained independently associated with DN. After an average follow-up of 2.5 (0.7) years, eGFR decline was greater in OSA⁺ compared with OSA⁻ patients (median −6.8% [interquartile range −16.1 to 2.2] vs. −1.6% [−7.7 to 5.3%], P = 0.002). After adjusting, both baseline OSA (B = −3.8, P = 0.044) and AHI (B = −4.6, P = 0.02) remained independent predictors of study-end eGFR. Baseline serum nitrotyrosine abundance (B = −0.24, P = 0.015) was an independent predictor of study-end eGFR after adjustment.

CONCLUSIONS

OSA is independently associated with DN in type 2 diabetes. eGFR declined faster in patients with OSA. Nitrosative stress may provide a pathogenetic link between OSA and DN. Interventional studies assessing the impact of OSA treatment on DN are needed.Diabetic nephropathy (DN) is the most common cause of end-stage renal disease (ESRD) in many countries (1) and has significant impact on patients and health care systems (2). DN progresses slowly, starting with microalbuminuria, which progresses into overt proteinuria in 20–40% of patients, and 20% of patients will have progressed to ESRD within 20 years after onset of overt proteinuria (1). The speed of DN progression is variable and largely dependent on blood pressure (BP), obesity, metabolic control, and other factors such as male sex and ethnicity (3,4).The pathogenesis of DN is thought to be similar to other microvascular complications in which hyperglycemia and hypertension are thought to be fundamental to its development, as they promote increased oxidative and nitrosative stress (3). In addition, hemodynamic changes occur as a result of the activation of the renin-angiotensin-aldosterone (RAAS) and endothelin systems, resulting in increased systemic and intraglomerular pressure, causing hyperfiltration and albuminuria (3). Despite attempts to improve metabolic control and RAAS inhibition, DN remains very common, and many patients develop ESRD requiring renal replacement therapy. Hence, better understanding of the pathogenesis of DN is needed in order to develop more effective treatments.Several reports, including our own, have shown a high prevalence of obstructive sleep apnea (OSA) in patients with type 2 diabetes (5,6). Patients with OSA and type 2 diabetes are at increased risk of diabetic peripheral neuropathy (6). Furthermore, OSA is associated with increased oxidative and nitrosative stress as well as impaired microvascular regulation in patients with type 2 diabetes (6). Hence, it is plausible that OSA complicating type 2 diabetes could facilitate the development and progression of microvascular complications including DN.The primary aims of this study were to assess the relationship between OSA and DN and to assess the impact of OSA on the estimated glomerular filtration (eGFR) decline in patients with type 2 diabetes. Secondary aims were to assess the impact of OSA on the development of albuminuria and to explore the mechanisms by which OSA and DN could be linked.     

Analysis of serum metabolomics among biopsy-proven diabetic nephropathy,type 2 diabetes mellitus and healthy controls

Type 2 diabetes mellitus (T₂DM) has a rising prevalence and diabetic nephropathy (DN) is a major complication of T₂DM. Metabolomics could provide novel insights into the pathogenesis, so we aimed to explore serum metabolomic profiles from DN to T₂DM. Serum samples were collected from 14 biopsy-proven DNs, 14 age/gender-matched T₂DMs without renal diseases (DM), 14 age/gender-matched healthy controls (CTRL) and household contacts of DM group (HH). Serum metabolomics was analyzed by untargeted liquid chromatography-tandem mass spectrometry (LC/MS) assays. There were a total of 1470 metabolites identified from all serum samples. 45 metabolites with significantly different intensity were found between DN and DM, e.g., biliverdin and taurine were reduced while l-arginine was increased in DN comparing to DM. DN could be distinguished from age/gender matched DM patients by l-arginine (AUC = 0.824) or taurine levels (AUC = 0.789). The metabolic pathways affected by metabolite distinctions between DN and DM also existed, among which taurine and hypotaurine metabolism exhibited the highest pathway impact. l-Methionine, deethylatrazine, l-tryptophan and fumaric acid were reduced in DM comparing with those of CTRL, but had no different intensity in DM and HH groups. The changes were demonstrated in the metabolomic profiles of biopsy-proven DN compared to DM. Biopsy-proven DN patients could be distinguished from age/gender matched DM by l-arginine or taurine levels in serum metabolomic profiles. Taurine and hypotaurine metabolism pathway had the highest impact in pathway set enrichment analysis, which potentially affected the pathogenesis of DN from T₂DM.

Metabolites between healthy controls (CTRL)/type 2 diabetes mellitus without renal diseases (DM), and DM/diabetic nephropathy (DN).     

Correlations of six related purine metabolites and diabetic nephropathy in Chinese type 2 diabetic patients

Objectives

The assessment of the clinical significance of adenosine, adenine, inosine, xanthine, hypoxanthine and uric acid concentrations in patients with type 2 diabetes mellitus (T2DM) and diabetic nephropathy (DN) for the detection of the relationship between purine metabolites and disease.

Design and methods

The study group consisted of 119 subjects which were divided into three groups: control (n = 31), type 2 diabetes without nephropathy (DM, n = 23) and with nephropathy (DN, n = 65). Levels of related metabolites were measured in plasma of all participants.

Results

There is a significant increase of levels of adenosine (P < 0.001), inosine (P < 0.001), xanthine (P = 0.012) and uric acid (P = 0.016) with DN compared to DM. The level of xanthine oxidase (reflected by the uric acid: xanthine) did not change.

Conclusion

The levels of adenosine, inosine, uric acid and xanthine may be useful for monitoring the progression of DM and evaluating the treatment.     

The fecal metabolome is associated with gestational diabetes mellitus

Dysbiosis of gut microbiota has been linked to gestational diabetes mellitus (GDM), and grows as a resource for GDM biomarkers. However, the contributions of gut microbiota to GDM remain incompletely understood. Metabolites are key messengers in the interactions between gut microbiota and the host. Metabolomics is emerging as an essential tool in exploring the contributions of gut microbiota to diseases. In this study, we performed ¹H-NMR based metabolomics on the feces of 62 pregnant women, including 31 women with GDM, and 31 women as the non-diabetes (NDM) control. Using Principle Component Analysis (PCA) and Orthogonal Projection to Latent Structures Discrimination Analysis (OPLS-DA), we observed clear cluster separation of the fecal metabolome between women with GDM and the NDM control. We further applied several feature selection methods to find five fecal metabolites contributing to the cluster separation of the fecal metabolome. These five metabolites, namely dibutyl decanedioate, N-acetylgalactosamine-4-sulphate, homocysteine, l-malic acid, and butanone, were significantly correlated with the clinical indices of GDM. Metabolite enrichment and pathway analysis on the five metabolites suggested that the fecal citrate cycle and sulfur metabolism were correlated with GDM. The results of this study demonstrated that disorders in the fecal metabolome are associated with GDM.

Fecal metabolome could separate women with GDM from the non-diabetic control.     

A metabolic profiling analysis of symptomatic gout in human serum and urine using high performance liquid chromatography-diode array detector technique

BackgroundUric acid (UA) is the only biomedical indicator for gout in clinic that always leads to an uncertain diagnose. Due to the lack of reliable metabolites, it is now already highly desirable to diagnose gout definitely.MethodsMetabonomics was employed to screen and identify novel biomarkers of gout based on human serum and urine. High performance liquid chromatography-diode array detector (HPLC-DAD) and orthogonal signal correction partial least squares discriminate analysis (OSC-PLS-DA) were also used for metabonomics study.ResultsSeveral potential biomarkers including uric acid, creatinine, tryptophan in serum and uric acid, creatinine, guanosine, hippuric acid in urine, were respectively screened and identified. For serum and urine, the predictive levels about the OSC-PLS-DA models of the gout and controls were 95.76% and 100%, and the correction levels about the seriousness of the disease were 90.32% and 87.5%, respectively.ConclusionCompared with intermittent gout, the acute gout shows clearly the dysfunctions of purine, protein and glucose metabolism. The metabolizing of guanosine to UA increases the levels of UA in serum at the acute stage. Our research contributes to a better understanding of the metabolic mechanism and allowing the targeted therapy of gout at different stages.     

Exploring the pharmacological effects and potential targets of paeoniflorin on the endometriosis of cold coagulation and blood stasis model rats by ultra-performance liquid chromatography tandem mass spectrometry with a pattern recognition approach

This study was employed to explore the potential biomarkers of endometriosis of cold coagulation and blood stasis (ECB) model rats and the effective mechanism of action of paeoniflorin (PF). The serum metabolomics approach was carried out using the UPLC-MS technique with a pattern recognition approach to prove the possible biomarkers of the ECB model rats and the perturbed pathways. Subsequently, the mechanism of PF treatment of this disease model was elucidated. The results revealed that the serum metabolism profiles in two groups were also separated significantly. Moreover, 8 biomarkers were found in the positive mode, and 5 biomarkers were found in the negative mode. Totally, 13 biomarkers participated in the metabolism of phenylalanine, arachidonic acid, etc. After treatment with PF, 10 biomarkers were regulated. Among the 10 biomarkers, 4 were statistically significant: l-phenylalanine, l-tryptophan, LysoPC (18:4(6Z,9Z,12Z,15Z)), and LysoPC (16:1(9Z)). We initially confirmed that PF could significantly regulate the metabolic expression of multiple metabolic pathways in the ECB model rats. For the first time, this study explored the mechanism of action of PF treatment based on the metabolic pathways of the organism and demonstrated the potential of the metabolomics techniques for the study of drug action mechanisms.

This study was employed to explore the potential biomarkers of endometriosis of cold coagulation and blood stasis (ECB) model rats and the effective mechanism of action of paeoniflorin (PF).     

Elevation of serum pyruvate kinase M2 (PKM2) in IBD and its relationship to IBD indices

ObjectivesEndoscopy remains the gold standard to diagnose and evaluate inflammatory bowel disease (IBD) activity. Current biomarkers or their combinations cannot adequately predict IBD risk, diagnosis, progression or relapse, and response to therapy. Pyruvate kinase M2 (PKM2) is emerging as a significant mediator of the inflammatory process. We aimed to assess levels of serum PKM2 in healthy and newly diagnosed IBD patients and its relationship with IBD indices and microbiota changes.Design and methodsIBD serum samples from newly diagnosed patients were collected and analyzed using a PKM2-ELISA and correlated with disease activity scores, IBD disease type, and intestinal microbiota. Furthermore, we tested the genetic and protein expression of PKM2 in an in vitro intestinal cell model of inflammation.ResultsSerum PKM2 levels were 6-fold higher in IBD patients compared to healthy controls, with no sensitivity to disease phenotype (Crohn's Disease or Ulcerative Colitis) or localization of inflammation. Serum PKM2 had considerably less interindividual variability than established IBD fecal biomarkers. A positive Pearson correlation (r = 0.6121) existed between serum PKM2 and Bacteroidetes fecal levels in Crohn's disease (CD), while a negative (r = − 0.6128) correlation was observed with Actinobacteria fecal levels. Furthermore, LPS (500 ng/mL) significantly increased PKM2 expression in vitro, which was significantly suppressed by an anti-inflammatory flaxseed bioactive agent.ConclusionOur data suggests PKM2 as a putative biomarker for IBD and the dysbiosis of microflora in CD. Investigations involving larger number of clinical patients are necessary to validate its use as a serum biomarker of IBD.