Serum and urine metabolomics study reveals a distinct diagnostic model for cancer cachexia.

BACKGROUND: Cachexia is a multifactorial metabolic syndrome with high morbidity and mortality in patients with advanced cancer. The diagnosis of cancer cachexia depends on objective measures of clinical symptoms and a history of weight loss, which lag behind disease progression and have limited utility for the early diagnosis of cancer cachexia. In this study, we performed a nuclear magnetic resonance-based metabolomics analysis to reveal the metabolic profile of cancer cachexia and establish a diagnostic model. METHODS: Eighty-four cancer cachexia patients, 33 pre-cachectic patients, 105 weight-stable cancer patients, and 74 healthy controls were included in the training and validation sets. Comparative analysis was used to elucidate the distinct metabolites of cancer cachexia, while metabolic pathway analysis was employed to elucidate reprogramming pathways. Random forest, logistic regression, and receiver operating characteristic analyses were used to select and validate the biomarker metabolites and establish a diagnostic model. RESULTS: Forty-six cancer cachexia patients, 22 pre-cachectic patients, 68 weight-stable cancer patients, and 48 healthy controls were included in the training set, and 38 cancer cachexia patients, 11 pre-cachectic patients, 37 weight-stable cancer patients, and 26 healthy controls were included in the validation set. All four groups were age-matched and sex-matched in the training set. Metabolomics analysis showed a clear separation of the four groups. Overall, 45 metabolites and 18 metabolic pathways were associated with cancer cachexia. Using random forest analysis, 15 of these metabolites were identified as highly discriminating between disease states. Logistic regression and receiver operating characteristic analyses were used to create a distinct diagnostic model with an area under the curve of 0.991 based on three metabolites. The diagnostic equation was Logit(P) = -400.53 - 481.88 × log(Carnosine) -239.02 × log(Leucine) + 383.92 × log(Phenyl acetate), and the result showed 94.64% accuracy in the validation set. CONCLUSIONS: This metabolomics study revealed a distinct metabolic profile of cancer cachexia and established and validated a diagnostic model. This research provided a feasible diagnostic tool for identifying at-risk populations through the detection of serum metabolites.

Plasma, urine and ligament tissue metabolite profiling reveals potential biomarkers of ankylosing spondylitis using NMR-based metabolic profiles.

BACKGROUND: Ankylosing spondylitis (AS) is an autoimmune rheumatic disease mostly affecting the axial skeleton. Currently, anti-tumour necrosis factor α (anti-TNF-α) represents an effective treatment for AS that may delay the progression of the disease and alleviate the symptoms if the diagnosis can be made early. Unfortunately, effective diagnostic biomarkers for AS are still lacking; therefore, most patients with AS do not receive timely and effective treatment. The intent of this study was to determine several key metabolites as potential biomarkers of AS using metabolomic methods to facilitate the early diagnosis of AS. METHODS: First, we collected samples of plasma, urine, and ligament tissue around the hip joint from AS and control groups. The samples were examined by nuclear magnetic resonance spectrometry, and multivariate data analysis was performed to find metabolites that differed between the groups. Subsequently, according to the correlation coefficients, variable importance for the projection (VIP) and P values of the metabolites obtained in the multivariate data analysis, the most crucial metabolites were selected as potential biomarkers of AS. Finally, metabolic pathways involving the potential biomarkers were determined using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, and the metabolic pathway map was drawn. RESULTS: Forty-four patients with AS agreed to provide plasma and urine samples, and 30 provided ligament tissue samples. An equal number of volunteers were recruited for the control group. Multidimensional statistical analysis suggested significant differences between the patients with AS and control subjects, and the models exhibited good discrimination and predictive ability. A total of 20 different metabolites ultimately met the requirements for potential biomarkers. According to KEGG analysis, these marker metabolites were primarily related to fat metabolism, intestinal microbial metabolism, glucose metabolism and choline metabolism pathways, and they were also probably associated with immune regulation. CONCLUSIONS: Our work demonstrates that the potential biomarkers that were identified appeared to have diagnostic value for AS and deserve to be further investigated. In addition, this work also suggests that the metabolomic profiling approach is a promising screening tool for the diagnosis of patients with AS.

Analysis of metabolic characteristics in a rat model of chronic pancreatitis using high-resolution magic-angle spinning nuclear magnetic resonance spectroscopy.

Pathological and metabolic alterations co-exist and co-develop in the progression of chronic pancreatitis (CP). The aim of the present study was to investigate the metabolic characteristics and disease severity of a rat model of CP in order to determine associations in the observed pathology and the metabolites of CP using high-resolution magic-angle spinning nuclear magnetic resonance spectroscopy (HR-MAS NMR). Wistar rats (n=36) were randomly assigned into 6 groups (n=6 per group). CP was established by administering dibutyltin dichloride solution into the tail vein. After 0, 7, 14, 21, 28 and 35 days, the pancreatic tissues were collected for pathological scoring or for HR-MAS NMR. Correlation analyses between the major pathological scores and the integral areas of the major metabolites were determined. The most representative metabolites, aspartate, betaine and fatty acids, were identified as possessing the greatest discriminatory significance. The Spearman's rank correlation coefficients between the pathology and metabolites of the pancreatic tissues were as follows: Betaine and fibrosis, 0.454 (P=0.044); betaine and inflammatory cell infiltration, 0.716 (P=0.0001); aspartate and fibrosis, -0.768 (P=0.0001); aspartate and inflammatory cell infiltration, -0.394 (P=0.085); fatty acid and fibrosis, -0.764 (P=0.0001); and fatty acid and inflammatory cell infiltration, -0.619 (P=0.004). The metabolite betaine positively correlated with fibrosis and inflammatory cell infiltration in CP. In addition, aspartate negatively correlated with fibrosis, but exhibited no significant correlation with inflammatory cell infiltration. Furthermore, the presence of fatty acids negatively correlated with fibrosis and inflammatory cell infiltration in CP. HR-MAS NMR may be used to analyze metabolic characteristics in a rat model of different degrees of chronic pancreatitis.

Metabolic characteristics of acute necrotizing pancreatitis and chronic pancreatitis.

The etiology and pathogenesis of pancreatitis remains unclear. In the presence of pancreatic inflammation, metabolite abnormalities appear before transformation of tissue structure and changes in functions occur. Detection of abnormalities in metabolite levels facilitates a greater understanding of the pathophysiological events and aids in the early diagnosis of the disease. In this study, metabolic profiles from the pancreas of Wistar rats were examined using high-resolution proton magic angle spinning nuclear magnetic resonance (MAS NMR) spectroscopy to investigate the metabolite indicator(s) of acute necrotizing pancreatitis (ANP) and chronic pancreatitis (CP). The animals were divided into three groups: those with histologically confirmed ANP (n = 7), those with CP (n = 6) and a control group (n = 9). The processed NMR spectra were analyzed using principal component analysis (PCA) to extract characteristic metabolites of ANP and CP. Levels of leucine, isoleucine and valine were increased in the ANP group, whereas an opposite trend was observed in the CP group. Increases in phosphocholine, glycerophosphocholine and choline levels, and decreases in fatty acids, lactate, betaine and glycine levels were observed in both the ANP and CP groups. Additionally, the lipid content in the CP group was higher than that observed in the ANP group. An increase in taurine levels was observed only in the CP group. In conclusion, pancreatitis causes a disruption of the metabolism in the pancreas at a molecular level, with increased taurine levels being a potential metabolite indicator for those with CP.

Proline-containing cyclopeptides from the marine sponge Phakellia fusca.

Four new cyclopeptides, phakellistatins 15-18 (2-5), together with five known cyclopeptides, phakellistatin 13 (1), hymenistatin 1, and hymenamides G, H, and J, were isolated from the South China Sea sponge Phakellia fusca. Their structures were elucidated by HR-ESIMS, NMR, and MALDI-TOF/TOF sequence analysis. The absolute configurations of the amino acid residues of 2-5 were assigned to be l by enantioselective HPLC analysis.

A metabonomic approach to early prognostic evaluation of experimental sepsis by (1)H NMR and pattern recognition.

This study proposes an NMR-based metabonomic approach to early prognostic evaluation of sepsis. Forty septic rats receiving cecal ligation and puncture (CLP) were divided into the surviving group and nonsurviving group on day 6, while 20 sham-operated rats served as the control group. Serum samples were collected from septic and sham-operated rats at 12 h after surgery and analyzed using (1)H NMR spectroscopy. Orthogonal partial least squares (OPLS) were applied and showed clustering according to predefined groups, indicating that NMR-based metabolic profiling could reveal pathologic characteristics in the serum of sham-operated, surviving, and nonsurviving septic rats. In addition, six characteristic metabolites including lactate, alanine, acetate, acetoacetate, hydroxybutyrate, and formate, which are mainly involved in energy metabolism, changed markedly in septic rats, especially in the nonsurvivors. Using these metabolites, a predictive model for prognostic evaluation of sepsis was constructed using a radial basis function neural network (RBFNN) with a prediction accuracy of about 87% by test samples. The results indicated that the NMR-based metabonomic approach is a potential technique for the early prognostic evaluation of sepsis.

Saponins from Polygala japonica and their effects on a forced swimming test in mice.

Five new triterpenoid saponins, polygalasaponins E (1), F (2), G (3), H (4), and J (5), along with eight known ones (6-13), were isolated from the aerial parts of Polygala japonica. Their structures were established by chemical and spectroscopic means. Forced swimming tests on mice showed that saponins 1 and 4 significantly reduce the immobility status by 58.1% and 51.3% at a dosage of 100 mg/kg administrated orally once daily for 5 days, respectively.

Two new iridoids from Patrinia scabra.

From the roots of Patrinia scabra two new iridoids, 3-methylbutyric acid 7-hydroxy-7-hydroxymethyl-4-(3-methyl-butyryloxymethyl)-6-oxo-1,6,7,7a-tetrahydrocyclopenta[c]pyran-1-yl ester (1) and 6-hydroxy-7-methylhexahydrocyclopenta[c]pyran-3-one (2) have been isolated. Their structures were determined by means of NMR spectra and X-ray crystallographic analysis.

[Two new C21 steroidal glycosides from Marsdenia tenacissima].

AIM: To study the chemical constituents of Marsdenia tenacissima (Roxb.) Wight et Arn. METHODS: To separate compounds with various chromatography technology and to elucidate their structures by chemical and spectral analysis. RESULTS: Two compounds were isolated from Marsdenia tenacissima and their stuctures were determined as tenacissosides J (I) and tenacissosides K (II). CONCLUSION: Compounds I and II are new C21 steroidal glycosides.

[Convolution spectrometric determination of the effect of hydroxyl radical scavenger on UV radiation-induced DNA aberrance].

Convolution spectrometry was applied to determining the DNA aberrance induced by UV-A, UV-B and UV-C radiation, and the extent of minute aberrance was quantitatively expressed by the differential value of convolution spectra. The differential values of DNA solutions irradiated by UV-A, UV-B and UV-C increase in turn, indicating an increscent DNA aberrance. The addition of dimethylsulfoxide or mannitol to DNA solution decreases the differential value in respective way under UV-A, UV-B and UV-C radiation, representing different inhibitory effects. Dimethylsulfoxide decreases the UV-A-induced DNA aberrance by 60% (approximate value), UV-C-induced aberrance by 35% (approximate value), and UV-B-induced aberrance by 20% (approximate value), while mannitol shows similar inhibitory effects (40%, approximate value) for UV-A, UV-B and UV-C-induced DNA aberrance. Although the extent of DNA aberrance varies, the distribution of differential points of convolution spectra reveals that the types of UV radiation-induced DNA aberrance are similar, and the inhibitory mechanism of two hydroxyl radical scavengers is possibly the same.

[A new alkaloids isolated from tetraploidy banlangen].

AIM: To investigate the chemical constituents of tetraploidy Banlangen (Isatis indigotica Fort.). METHODS: Compounds were separated by chromatography on silica gel. Their structures were determined by spectral analysis and chemical evidence. RESULTS: Three compounds were isolated. Their structures were identified as (E)-2-[(3'-indole) cyanomethylene]-3-indolinone (I), 2-(4-hydroxy-3-methoxyphenyl)-4-[(4-hydroxy-3-methoxy-phenyl)-methyl]-3- hydroxymethyl-tetrahydro-furan (II) and 2-methoxy-4-[tetrahydro-4-[(4-hydroxy-3-methoxy-phenyl)-methyl]-3- hydroxymethyl-2-furanyl] phenyl-1-O-beta-D-glucopyranoside (III). CONCLUSION: Compound I is a new compound.