[Investigation of Evolution Rules of Phlegm and Blood Stasis Syndrome in Hyperlipidemia and Ath- erosclerosis by NMR-based Metabolic Profiling and Metabonomic Approaches].

Objective: To explore evolution rules of phlegm and blood stasis syndrome ( PBSS) in hyperlipidemia and atherosclerosis (AS) using NMR-based metabolic profiling and metabonomic approaches based on formulas corresponding to syndrome.

Methods: Totally 150 SD rats were divided into the normal group, the model group, the Erchen Decoction (ED) group, the Xuefu Zhuyu Decoction (XZD) group, the Lipitor group, 30 in each group. The hyperlipidemia and AS rat model was duplicated by suturing carotid artery, injecting vitamin D3, and feeding with high fat diet.

An integrated metabonomic and proteomic study on Kidney-Yin Deficiency Syndrome patients with diabetes mellitus in China.

Aim: To investigate specific changes in metabolites and proteins of Kidney-Yin Deficiency Syndrome (KYDS) patients with diabetes mellitus (DM) in China.

Methods: KYDS (n=29) and non-KYDS (n=23) patients with DM were recruited for this study. The KYDS was diagnosed by two senior TCM clinicians separately.

Metabolomic Profiling of Autoimmune Hepatitis: The Diagnostic Utility of Nuclear Magnetic Resonance Spectroscopy.

Autoimmune hepatitis (AIH) is often confused with other liver diseases because of their shared nonspecific symptoms and serological and histological overlap. This study compared the plasma metabolomic profiles of patients with AIH, primary biliary cirrhosis (PBC), PBC/AIH overlap syndrome (OS), and drug-induced liver injury (DILI) with those of healthy subjects to identify potential biomarkers of AIH. Metabolomic profiling and biomarker screening were performed using proton nuclear magnetic resonance spectroscopy (H NMR) coupled with a partial least-squares discriminant analysis.

Revealing metabolite biomarkers for acupuncture treatment by linear programming based feature selection.

Background: Acupuncture has been practiced in China for thousands of years as part of the Traditional Chinese Medicine (TCM) and has gradually accepted in western countries as an alternative or complementary treatment. However, the underlying mechanism of acupuncture, especially whether there exists any difference between varies acupoints, remains largely unknown, which hinders its widespread use.

Results: In this study, we develop a novel Linear Programming based Feature Selection method (LPFS) to understand the mechanism of acupuncture effect, at molecular level, by revealing the metabolite biomarkers for acupuncture treatment.

[Efficacy of lamivudine on acute-on-chronic liver failure in patients with chronic hepatitis B].

To observe the therapeutic effects of lamivudine treatment in patients with early- to mid-stage hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF). Clinical data of 73 hospitalized patients with HBV-ACLF were retrospectively analyzed. Prothrombin time (PT, active coagulation), HBV DNA, and model for end-stage liver disease (MELD) score data from treatment weeks 4, 8, 24, and 48 were collected and analyzed using the statistical t-test.

Metabolomic analysis of biochemical changes in the plasma and urine of first-episode neuroleptic-naïve schizophrenia patients after treatment with risperidone.

Early findings propose that impaired neurotransmission in the brain plays a key role in the pathophysiology of schizophrenia. Recent advances in understanding its multiple etiologies and pathogenetic mechanisms provide more speculative hypotheses focused on even broader somatic systems. Using a targeted tandem mass spectrometry (MS/MS)-based metabolomic platform, we compared metabolic signatures consisting of monoamine and amino acid neurotransmitter (NT) metabolites in plasma/urine simultaneously between first-episode neuroleptic-naïve schizophrenia patients (FENNS) and healthy controls before and after a 6-week risperidone monotherapy, which suggest that the patient NT profiles are restoring during treatment.

Comparative study on effects of Xiaoyao Powder and its modified prescription on plasma metabolomics of rats with chronic immobilization stress.

Objective: To determine the changes in the levels of endogenous metabolites in rats with chronic immobilization stress (CIS) taking Xiaoyao Powder (XYP) and its modified prescription version, which lacks the volatile oils extracted from Herba Menthae.

Methods: Twenty-four experimental male SD rats were randomly divided into 4 groups of 6 rats each: control, model, XYP-1 (containing volatile oils from Herba Menthae), and XYP-2 (lacking volatile oils). All rats except control group rats were subjected to CIS 3 h per day for 21 consecutive days.

[Primary anylasis on the methodology and strategies for studying mechanisms of acu-moxibustion by using metabonomics].

Metabonomics is a newly emerging modern technology in the Post-genome era and has been being used widely in the study on modern Chinese medicine. But it have been rarely used in the study on acupuncture therapy. In the present paper, the authors introduce the unique advantages of metabonomics in the systemtic biology and its widespread studying basis in the field of modern Chinese medicine.

A(1)H NMR-based metabonomic study on the SAMP8 and SAMR1 mice and the effect of electro-acupuncture.

A (1)H NMR-based metabonomic method was used to investigate the metabolic change of plasma in senescence-prone 8 (SAMP8) mice before and after electro-acupuncture (EA). Sixteen SAMP8 male mice (aged 8 months) were randomly divided into model group and acupuncture treatment group while the later group received EA treatment for 21 days. Eight senescence-resistant 1 (SAMR1) mice were used as the control group.

Interaction with polyglutamine-expanded huntingtin alters cellular distribution and RNA processing of huntingtin yeast two-hybrid protein A (HYPA).

Huntington disease (HD) is an autosomal inherited disorder that causes the deterioration of brain cells. The polyglutamine (polyQ) expansion of huntingtin (Htt) is implicated in the pathogenesis of HD via interaction with an RNA splicing factor, Htt yeast two-hybrid protein A/forming-binding protein 11 (HYPA/FBP11). Besides the pathogenic polyQ expansion, Htt also contains a proline-rich region (PRR) located exactly in the C terminus to the polyQ tract.

[Effects of electroacupuncture of "Weishu" (BL 21) and "Zhongwan" (CV 12) on serum large molecular metabolites in functional dyspepsia rats].

Objective: To compare the effects of electroacupuncture (EA) of Shu-acupoint "Weishu" (BL 21), Mu-acupoint "Zhongwan" (CV 12) and BL 21 + CV 12 on serum large molecular metabolites in functional dyspepsia (FD) rats.

Methods: A total of 50 Wistar rats were randomly divided into control, model, BL 21, CV 12 and BL 21 + CV 12 groups (n = 10/group). FD model was established by clamping the rats' tails for 30 min, once every 3 h, 4 times daily for 7 days.

[Nephrotoxicity study of Aristolochia fangchi in rats by metabonomics].

Objective: To study the changes of metabolites in rat urine after treatment of Aristolochia fangchi decoction by metabonomic method.

Methods: Sixty-four male SD rats were divided into Aristolochia fangchi group and normal control group. Rats in the Aristolochia fangchi group were orally administered with 8.

[Effects of acute hypoxia on plasma metabolome in mice].

Aim: To explore the metabolic effects of acute hypoxia on mice plasma.

Methods: Fourteen mice were randomly divided into two groups: control and hypoxia group. The mice of hypoxia group were exposed to a simulated altitude of 6000 meters for 8 hours.

[Metabonomic profile of urine from rats administrated with different treatment period of rifampin].

Objective: To study the effect of rifampin (RFP) on the metabonomic profile of rat urine and its relationship with traditional toxicity evaluation of blood biochemical indicators and histopathology.

Methods: Thirty-six male Wistar rats were randomly divided into control group, 50 mg/kg RFP group, and 100 mg/kg RFP group, with 12 rats in each group. Rats in each group were given intragastric infusion with a daily dose of 0, 50 mg/kg RFP, and 100 mg/kg RFP for 3, 7, and 14 days, respectively.

[Metabonomics profile of urine from rats administrated with different treatment period of isoniazid].

Objective: To study the effect of different treatment period, of isoniazid (INH) on the metabonomic profile of rat urine and its relationship with traditional toxicity evaluation of blood biochemical indicators and histopathology and to explore the feasibility of metabonomics in the application of drug toxicity.

Methods: Sixty male Wistar rats were orally administrated with 0, 50, 100, 200, and 400 mg x kg(-1) INH for 3, 7, and 14 days, respectively. Rat urine was then collected and its 1H nuclear magnetic resonance (NMR) spectra were acquired.

[Metabonomic study of blood plasma in the assessment of liver graft function].

Objective: To access the capability of 1H nuclear magnetic resonance (NMR) -based metabonomics in the evaluation of graft function in the perioperation period of liver transplantation.

Methods: Plasma samples of 15 male primary hepatic carcinoma patients were collected for clinical biochemical analysis and 1H NMR spectroscopy 1 day before operation, 1 day and 1 week after the operation. The NMR data were analyzed using principal component analysis.

Different roles for two ubiquitin-like domains of ISG15 in protein modification.

ISG15 (interferon-stimulated gene 15) is a novel ubiquitin-like (UbL) modifier with two UbL domains in its architecture. We investigated different roles for the two UbL domains in protein modification by ISG15 (ISGylation) and the impact of Influenza B virus NS1 protein (NS1B) on regulation of the pathway. The results show that, although the C-terminal domain is sufficient to link ISG15 to UBE1L and UbcH8, the N-terminal domain is dispensable in the activation and transthiolation steps but required for efficient E3-mediated transfer of ISG15 from UbcH8 to its substrates.

NMR-spectroscopy-based metabonomic approach to the analysis of Bay41-4109, a novel anti-HBV compound, induced hepatotoxicity in rats.

An integrated metabonomics study using high-resolution (1)H nuclear magnetic resonance (NMR) spectroscopy has been applied to investigate the biochemical composition of urine, serum, liver tissue aqueous extracts (acetonitrile/water) and liver tissue lipidic extracts (chloroform/methanol) obtained from control and Bay41-4109 treated rats (10, 50, 400mg.kg(-1).d(-1) for 5 days, i.

Structural insights into the specific binding of huntingtin proline-rich region with the SH3 and WW domains.

The interactions of huntingtin (Htt) with the SH3 domain- or WW domain-containing proteins have been implicated in the pathogenesis of Huntington's disease (HD). We report the specific interactions of Htt proline-rich region (PRR) with the SH3GL3-SH3 domain and HYPA-WW1-2 domain pair by NMR. The results show that Htt PRR binds with the SH3 domain through nearly its entire chain, and that the binding region on the domain includes the canonical PxxP-binding site and the specificity pocket.

The NMR studies on two new furostanol saponins from Agave sisalana leaves.

The detailed NMR studies and full assignments of the 1H and 13C spectral data for two new furostanol saponins isolated from Agave sisalana leaves are described. Their structures were established using a combination of 1D and 2D NMR techniques including 1H, 13C, 1H-1H COSY, TOCSY, HSQC, HMBC and HSQC-TOCSY, and also FAB-MS spectrometry and chemical methods. The structures were established as (25S)-26-(beta-D-glucopyranosyl)-22 xi-hydroxyfurost-12-one-3beta-yl-O-alpha-L-rhamnopyranosyl-(1-->4)-beta-D-glucopyranosyl-(1-->3)-O-[O-beta-D-glucopyranosyl-(1-->2)]-O-beta-D-glucopyranosyl-(1-->4)-beta-D-galacto- pyranoside (1) and (25S)-26-(beta-D-glucopyranosyl)-22xi-hydroxyfurost-5-en-12-one-3beta-yl-O-alpha-L-rhamno- pyranosyl-(1-->4)-beta-D-glucopyranosyl-(1-->3)-O-[O-beta-D-glucopyranosyl-(1-->2)]-O-beta-D-glucopyranosyl- (1-->4)-beta-D-galactopyranoside (2).

Furostanol saponins from the fresh rhizomes of Polygonatum kingianum.

Ten furostanol saponins were isolated as five pairs of 25R and 25S epimers from the fresh rhizomes of Polygonatum kingianum. Seven of them were identified as new compounds, (25S)-kingianoside D (2), (25S)-kingiano-side C (4), (25R,22)-hydroxylwattinoside C (5), kingianoside E (7), (25S)-kingianoside E (8), kingianoside F (9) and (25S)-kingianoside F (10), together with three known saponins, kingianoside C (1), kingianoside D (3), and 22-hydroxylwattinoside C (6). The structures of the new saponins were determinded by detailed analysis of their 1D and 2D NMR spectra, and by comparison of the spectral data with those reported.

Highly efficient expression and purification system of small-size protein domains in Escherichia coli for biochemical characterization.

It is often essential to focus the study on the small-size domains of large proteins in eukaryotic cells in the post-genomic era, but the low expression level, insolubility, and instability of the domains have been continuing to hinder the massive purification of domain peptides for structural and biological investigation. In this work, a highly efficient expression and purification system based on a small-size fusion partner GB1 and histidine tag was utilized to solve these problems. Two vectors, namely pGBTNH and pGBH, were constructed to improve expression and facilitate purification.

Escherichia coli tRNA(4)(Arg)(UCU) induces a constrained conformation of the crucial Omega-loop of arginyl-tRNA synthetase.

Previous investigations show that tRNA(Arg)-induced conformational changes of arginyl-tRNA synthetase (ArgRS) Omega-loop region (Escherichia coli (E. coli), Ala451-Ala457) may contribute to the productive conformation of the enzyme catalytic core, and E. coli tRNA(2)(Arg)(ICG)-bound and -free conformations of the Omega-loop exchange at an intermediate rate on NMR timescale.

Substrate-induced conformational changes in Escherichia coli arginyl-tRNA synthetase observed by 19F NMR spectroscopy.

The 19F nuclear magnetic resonance (NMR) spectra of 4-fluorotryptophan (4-F-Trp)-labeled Escherichia coli arginyl-tRNA synthetase (ArgRS) show that there are distinct conformational changes in the catalytic core and tRNA anticodon stem and loop-binding domain of the enzyme, when arginine and tRNA(Arg) are added to the unliganded enzyme. We have assigned five fluorine resonances of 4-F-Trp residues (162, 172, 228, 349 and 446) in the spectrum of the fluorinated enzyme by site-directed mutagenesis. The local conformational changes of E.