Interplay between dietary intake, gut microbiota, and metabolic profile in obese adolescents: Sex-dependent differential patterns.

BACKGROUND & AIMS: The interplay among dietary intake, gut microbiota, gut metabolites and circulating metabolites in adolescents is barely known, not to mention sex-dependent pattern. We aimed to explore unique profiles of gut bacterial, gut metabolites and circulating metabolites from both genders of adolescents due to BMI and eating pattern. METHODS: Clinical indices, fecal gut microbiota, fecal and plasma metabolites, and diet intake information were collected in case-control sample matched for normal and obesity in girls (normal = 12, obesity = 12) and boys (normal = 20, obesity = 20), respectively. 16S rRNA gene sequencing and untargeted metabolomics was performed to analysis the signature of gut microbiota and metabolites. Unique profiles of girls associated with BMI and eating pattern was revealed by Spearman's correlations analysis, co-occurrence network analysis, Kruskal-Wallis test, and Wilcoxon rank-sum test. RESULTS: Gender difference was found between normal and obese adolescents in gut microbiota, fecal metabolites, and plasma metabolites. The Parabacteroides were only decreased in obese girls. And the characteristic of obese girls' and boys' cases in fecal and plasma was xanthine and glutamine, ornithine and LCA, respectively. Soy products intake was negatively associated with Parabacteroides. The predicted model has a higher accuracy based on the combined markers in obesity boys (AUC = 0.97) and girls (AUC = 0.97), respectively. CONCLUSIONS: Reduced abundance of Phascolarctobacterium and Parabacteroides, as well as the increased fecal xanthine and ornithine, may provide a novel biomarker signature in obesity girls and boys. Soy products intake was positively and negatively associated with Romboutsia and Parabacteroides abundance, respectively. And the combined markers facilitate the accuracy of predicting obesity in girls and boys in advance.

Effect of Sijunzi Pills on Pharmacokinetics of Omeprazole in Beagle Dogs by HPLC-UV: A Herb-Drug Interaction Study.

A sensitive high-performance liquid chromatography (HPLC-UV) method for determination of omeprazole in beagle dog plasma was developed and to investigate the effect of Sijunzi pills (SJZPs) on the pharmacokinetics of omeprazole in beagle dogs. The beagle dog plasma was extracted with ethyl acetate and n-hexane under alkaline conditions. Omeprazole and internal standard (IS, fluconazole) were separated on an XDB-C18 column, and acetonitrile and 0.1% trifluoroacetic acid were used as the mobile phase. Omeprazole and IS were detected by using a diode array detector. This experiment adopts the experimental design of double-cycle self-control. In the first cycle (group A), six beagle dogs were given omeprazole 0.67 mg/kg orally in a single dose. In the second period (group B), the same six beagle dogs were orally given SJZPs 0.2 g/kg twice a day for 7 consecutive days, and then, omeprazole was orally given. At the different time points after omeprazole was given in the two periods, the blood samples were collected. The concentration of omeprazole was detected by the developed HPLC method. DAS 2.0 was used to calculate the pharmacokinetic parameters of omeprazole. Under the current experimental conditions, this UPLC method showed good linearity in the detection of omeprazole. Interday and intraday precision did not exceed 10%, and the range of accuracy values were from -1.43% to 2.76%. The results of extraction recovery and stability met the requirements of FDA approval guidelines of bioanalytical method validation. The C max of omeprazole in group B was 61.55% higher than that in group A, and the AUC(0-t) and AUC(0-∞) of omeprazole in group B were 63.96% and 63.65% higher those that in group A, respectively. At the same time, the clearance (CL) and apparent volume of distribution (Vd) decreased in group B. In this study, an HPLC method for the determination of plasma omeprazole concentration was established. SJZPs could inhibit the metabolism of omeprazole and increase the concentration of omeprazole in beagle dogs. It is suggested that when SJZPs are combined with omeprazole, attention should be paid to the herb-drug interactions and possible adverse reactions.

Identification of a Novel Alternative Splicing Variant of VvPMA1 in Grape Root under Salinity.

It has been well-demonstrated that the control of plasma membrane H+-ATPase (PM H+-ATPase) activity is important to plant salt tolerance. This study found a significant increase in PM H+-ATPase (PMA) activity in grape root exposed to NaCl. Furthermore, 7 Vitis vinifera PM H+-ATPase genes (VvPMAs) were identified within the grape genome and the expression response of these VvPMAs in grape root under salinity was analyzed. Two VvPMAs (VvPMA1 and VvPMA3) were expressed more strongly in roots than the other five VvPMAs. Moreover, roots exhibited diverse patterns of gene expression of VvPMA1 and VvPMA3 responses to salt stress. Interestingly, two transcripts of VvPMA1, which were created through alternative splicing (AS), were discovered and isolated from salt stressed root. Comparing the two VvPMA1 cDNA sequences (designated VvPMA1α and VvPMA1ß) with the genomic sequence revealed that the second intron was retained in the VvPMA1ß cDNA. This intron retention was predicted to generate a novel VvPMA1 through N-terminal truncation because of a 5'- terminal frame shift. Yeast complementation assays of the two splice variants showed that VvPMA1ß could enhance the ability to complement Saccharomyces cerevisiae deficient in PM H+-ATPase activity. In addition, the expression profiles of VvPMA1α and VvPMA1ß differed under salinity. Our data suggests that through AS, the N-terminal length of VvPMA1 may be regulated to accurately modulate PM H+-ATPase activity of grape root in salt stress.

The role of dopamine receptors in ventrolateral orbital cortex-evoked antinociception in a rat formalin test model.

The present study examined the roles of dopamine and D(1)- and D(2)-like dopamine receptors in ventrolateral orbital cortex (VLO)-evoked antinociception in rats with persistent inflammatory pain. Following formalin injection into the rat unilateral hindpaw pad, the effects of dopamine receptor agonist and antagonist microinjections into the VLO on nociceptive behavior were observed. Results demonstrated that VLO microinjection of the non-selective dopamine receptor agonist apomorphine (R(-)-apomorphine hydrochloride, 1.0, 2.5 and 5.0µg) depressed later-phase nociceptive behavior induced by formalin injection; this effect was attenuated by the D(2)-like dopamine receptor antagonist S(-)-raclopride(+)-tartrate salt (raclopride, 3.0µg), but not by the D(1)-like dopamine receptor antagonist R(+)-SCH-23390 hydrochloride (SCH-23390, 1.0µg). Apomorphine-induced antinociception was mimicked by microinjection of the D(2)-like dopamine receptor agonist (-)-quinpirole hydrochloride (2.0 and 5.0µg) into the same VLO site, and this effect was antagonized by raclopride (3.0µg). In addition, microinjection of the D(1)-like dopamine receptor agonist R(+)-SKF-38393 hydrochloride (5.0µg) had no effect on formalin-induced nociceptive behavior during the later phase. However, the D(1)-like dopamine receptor antagonist SCH-23390 (2.5, 5.0 and 10µg) depressed nociceptive behavior in a dose-dependent manner. These results suggested that dopamine mediated VLO-induced antinociception via different mechanisms in the persistent inflammatory pain model; D(2)-like receptors mediated dopamine-induced antinociception, while D(1)-like dopamine receptors exhibited tonic facilitatory action on nociceptive behavior, thereby blocking D(1)-like dopamine receptors could induce antinociception.

[Lung cancer diagnosis based on urinary modified nucleoside metabolic profiling].

OBJECTIVE: To study the feasibility of modified urinary nucleosides metabolic profiling on lung cancer diagnoses. METHODS: The modified urinary nucleosides metabolic profiling from 42 normal adults and 80 patients with lung cancer were determined by a coupled-column high performance liquid chromatography system. Partial least squares-discriminant analysis (PLS-DA) models were used to class differentiation between the lung cancer patients and controls and to discover potential biomarkers. RESULT: The PLS-DA model results showed that there was a clear differentiation between normal adults and lung cancers patients, with the value of prediction (Q2) equals to 0.744. CONCLUSION: Modified urinary nucleosides metabolic profiling method is useful for lung cancer diagnoses.

Urinary nucleosides as biological markers for patients with colorectal cancer.

AIM: Fourteen urinary nucleosides, primary degradation products of tRNA, were evaluated to know the potential as biological markers for patients with colorectal cancer. METHODS: The concentrations of 14 kinds of urinary nucleosides from 52 patients with colorectal cancer, 10 patients with intestinal villous adenoma and 60 healthy adults were determined by column switching high performance liquid chromatography method. RESULTS: The mean levels of 12 kinds of urinary nucleosides (except uridine and guanosine) in the patients with colorectal cancer were significantly higher than those in patients with intestinal villous adenoma or the healthy adults. Using the levels of 14 kinds of urinary nucleosides as the data vectors for principal component analysis, 71% (37/52) patients with colorectal cancer were correctly classified from healthy adults, in which the identification rate was much higher than that of CEA method (29%). Only 10% (1/10) of patients with intestinal villous adenoma were indistinguishable from patients with colorectal cancer. The levels of m1G, Pseu and m1A were positively related with tumor size and Duke's stages of colorectal cancer. When monitoring the changes in urinary nucleoside concentrations of patients with colorectal cancer associated with surgery, it was found that the overall correlations with clinical assessment were 84% (27/32) and 91% (10/11) in response group and progressive group, respectively. CONCLUSION: These findings indicate that urinary nucleosides determined by column switching high performance liquid chromatography method may be useful as biological markers for colorectal cancer.