Kuo Gao

Metabolomic identification of diagnostic plasma biomarkers in humans with chronic heart failure.

Chronic heart failure (CHF), as a progressive clinical syndrome, is characterized by failure of enough blood supply from the heart to meet the bodys metabolic demands, and there is intense interest in identifying novel biomarkers that could make contributions to the diagnosis of CHF. Metabolomics, compared with current diagnostic approaches, could investigate many metabolic perturbations within biological systems. The overarching goal of the work discussed here is to apply a high-throughput approach to identify metabolic signatures and plasma diagnostic biomarkers underlying CHF by 1H-NMR spectroscopy. Plasma samples from 39 patients with CHF and 15 controls were analyzed by NMR spectroscopy. After processing the data, orthogonal partial least square discriminant analysis (OPLS-DA) was performed. The statistical model revealed good explained variance and predictability, and the diagnostic performance assessed by leave-one-out analysis exhibited 92.31% sensitivity and 86.67% specificity. The OPLS-DA score plots of spectra revealed good separation between case and control on the level of metabolites, and multiple biochemical changes indicated hyperlipidemia, alteration of energy metabolism and other potential biological mechanisms underlying CHF. It was concluded that the NMR-based metabolomics approach demonstrated good performance to identify diagnostic plasma markers and provided new insights into metabolic process related to CHF.

Wnt/β-catenin coupled with HIF-1α/VEGF signaling pathways involved in galangin neurovascular unit protection from focal cerebral ischemia.

Microenvironmental regulation has become a promising strategy for complex disease treatment. The neurovascular unit (NVU), as the key structural basis to maintain an optimal brain microenvironment, has emerged as a new paradigm to understand the pathology of stroke. In this study, we investigated the effects of galangin, a natural flavonoid isolated from the rhizome of Alpina officinarum Hance, on NVU microenvironment improvement and associated signal pathways in rats impaired by middle cerebral artery occlusion (MCAO). Galangin ameliorated neurological scores, cerebral infarct volume and cerebral edema and reduced the concentration of Evans blue (EB) in brain tissue. NVU ultrastructural changes were also improved by galangin. RT-PCR and western blot revealed that galangin protected NVUs through the Wnt/β-catenin pathway coupled with HIF-1α and vascular endothelial growth factor (VEGF). VEGF and β-catenin could be the key nodes of these two coupled pathways. In conclusion, Galangin might function as an anti-ischemic stroke drug by improving the microenvironment of NVUs.

Significance of Resveratrol in Clinical Management of Chronic Diseases

Resveratrol could be beneficial to health and provides protection against a wide array of pathologies and age-associated problems, as evident from preclinical studies. However, a comparison of animal and human studies reveals that this dietary polyphenol cannot protect against metabolic diseases and their associated complications. The clinical outcomes are affected by many factors such as sample size. This article not only presents a comprehensive review of the current advances concerning the dose, the extent of absorption, interaction and toxicity of resveratrol in human studies, but also describes its therapeutic effects against several chronic diseases such as diabetes mellitus, obesity, cardiovascular diseases, cancer and aging and the related diseases.

Chinese Herbal Medicine in the Treatment of Chronic Heart Failure: Three-Stage Study Protocol for a Randomized Controlled Trial.

Background. Chinese herbal medicine (CHM) has been used in the treatment of chronic heart failure (CHF) for a long time. Treatment based on syndrome differentiation and the main characteristic of TCM is the fundamental principle of TCM practice. In this study protocol, we have designed a trial to assess the efficacy and safety of CHM on CHF based on syndrome differentiation. Methods/Design. This is a three-stage trial of CHM in the treatment of CHF. The first stage is a literature review aiming to explore the common syndromes of CHF. The second is a multicentral, randomized, placebo-controlled trial to evaluate the efficacy and safety of CHM for the treatment of CHF. The third is a multicentral, randomized controlled clinical trial aiming to make cost-effectiveness analysis and evaluate the feasibility, compliance, and universality of CHM on CHF. Discussion. This trial will evaluate the efficacy, safety, feasibility, compliance, and universality of CHM on CHF. The expected outcome is to provide evidence-based recommendations for CHM on CHF and develop a prescription of CHM in the treatment of CHF. This trial is registered with NCT01939236 (Stage Two of the whole trial).

The active ingredients of Jiang-Zhi-Ning: study of the Nelumbo nucifera alkaloids and their main bioactive metabolites.

The object of this study was to identify the major active ingredients of the Chinese Traditional Medicine Jiang-Zhi-Ning (JZN) based on the high performance liquid chromatography (HPLC) profiles of plasma samples obtained from beagle dogs at different times after intragastric administration of JZN, crude JZN extracts, different extracted fractions, different subfractions of the active fraction and different isolated ingredients. 2-Hydroxy-1-methoxyaporphin (2H1M), an alkaloid from Nelumbo nucifera, one of the herbs that make up JZN, was identified as the constituent showing the major pharmacodynamic effect. The major metabolites of 2H1M were analyzed and identified as N-demethyl-2-hydroxy-1-methoxyaporphine-2-O-glycuronic acid, 2-hydroxy-1-methoxy-aporphine-2-O-glycuronic acid and 2-hydroxy-1-methoxy-aporphine-2-O-sulphate. This study provided a comprehensive insight into the active components of JZN.

A dinuclear ruthenium(II) complex as turn-on luminescent probe for hypochlorous acid and its application for in vivo imaging.

A dinuclear ruthenium(II) complex Ruazo was designed and synthesized, in which oxidative cyclization of the azo and o-amino group was employed for the detection of hypochlorous acid (HClO) in aqueous solution. The non-emissive Ruazo formed highly luminescent triazole-ruthenium(II) complex in presence of HClO and successfully imaged HClO in living cell and living mouse.

Systems-biology dissection of mechanisms and chemical basis of herbal formula in treating chronic myocardial ischemia

Herbal medicine is a mixture of multiple compounds, and is intended to exhibit therapeutic effects by attacking multiple disease-causing modules simultaneously. However, it is still a challenge for scientists to untangle the complex biological mechanisms and underlying material basis of herbal medicine. Here, this study was designed to build a systems-biology platform for exploring the molecular mechanisms and corresponding active compounds, with a typical example applied to an herbal formula Qishenkel (QSKL) in the treatment of chronic myocardial ischemia. We have applied an approach integrating transcriptome sequencing, bioactivity profiling inference, computational ligand-receptor evaluation and experimental validation to study the effects on pig myocardial ischemia treated with QSKL. Numerous biological modules were revealed and indicated the coordinated regulation of molecular networks from various aspects of cardiac function. In addition, gene expression profiles were utilized to identify a number of key therapeutic targets of herbal formula, such as angiotensin-converting enzyme and calcium channels. Then, these therapeutic targets were used to fish the potential active ingredients based on a combination of target structure-based and chemical ligand-based methods. Some active compounds, including luteolin, cryptotanshinone, licochalcone A, glycyrrhetinic acid, salsolinol, isoacid chlorogenic C, salvianolic acid A and salvianolic acid B, have been validated by direct biochemical methods. This strategy integrating different types of technologies is expected to provide not only a detailed understanding about the combined therapeutic effects of herbal mixture but also a new opportunity for discovering novel natural molecules with pharmacological activities.

1-Deoxynojirimycin: Occurrence, Extraction, Chemistry, Oral Pharmacokinetics, Biological Activities and In Silico Target Fishing.

1-Deoxynojirimycin (DNJ, C6H13NO4, 163.17 g/mol), an alkaloid azasugar or iminosugar, is a biologically active natural compound that exists in mulberry leaves and Commelina communis (dayflower) as well as from several bacterial strains such as Bacillus and Streptomyces species. Deoxynojirimycin possesses antihyperglycemic, anti-obesity, and antiviral features. Therefore, the aim of this detailed review article is to summarize the existing knowledge on occurrence, extraction, purification, determination, chemistry, and bioactivities of DNJ, so that researchers may use it to explore future perspectives of research on DNJ. Moreover, possible molecular targets of DNJ will also be investigated using suitable in silico approach.

Papers published from 1995 to 2012 by six Traditional Chinese Medicine universities in China: a bibliometric analysis based on science citation index.

OBJECTIVE The quality and quantity of published research papers are important in both scientific and technology fields. Although there are several bibliometric studies based on citation analysis, very few have focused on research related to Traditional Chinese Medicine in China. METHODS The bibliometric method used in this study included the following focuses: publication outputs for each year, paper type, language of publication, distribution of internationally collaborative countries, sources of funding, authorization number, distribution of institutes regarding collaborative publications, research fields, distribution of outputs in journals, citation, data, and h-index. RESULTS A total of 3809 papers published from 1995 to 2012 were extracted from the science citation index (SCI). The cumulative number of papers from all six universities is constantly increasing. The United States attained the dominant position regarding complementary and alternative medicine research. The Chinese Academy of Sciences was the greatest participator in collaborative efforts. Research field analysis showed that the research mainly focused on pharmacology pharmacy, chemistry, integrative complementary medicine, plant sciences, and biochemistry molecular biology. The Shanghai University of Chinese Medicine had the most citations. CONCLUSION In recent years, in terms of SCI papers, the six Traditional Chinese Medicine universities studied here have made great advances in scientific research.

Metabolic effects of Hedyotis diffusa on rats bearing Walker 256 tumor revealed by NMR-based metabolomics.

Hedyotis diffusa, a traditional Chinese herbal medicine, is widely used for oncotherapy and shows a positive effect in the clinical treatment. But its mechanism of anticancer activities is complicated and unclear. This study was undertaken to assess the therapeutic effects and reveal detailed mechanisms of H. diffusa for oncotherapy. A Walker 256 tumor‐bearing rat model was established, and metabolomic profiles of plasma and urine were obtained from 1H NMR technique. Multivariate statistical analysis methods were used to characterize the discriminating metabolites between control (C), Walker 256 tumor‐bearing rats model (M), and H. diffusa treatment (H) groups. Finally, 13 and 10 metabolomic biomarkers in urine and plasma samples were further identified as characteristic metabolites in M group, whereas H group showed a partial metabolic balance recovered, such as ornithine, N‐acetyl‐l‐aspartate, l‐aspartate, and creatinine in urine samples, and acetate, lactate, choline, l‐glutamine, and 3‐hydroxybutyrate in plasma samples. On the basis of the methods above, we hypothesized H. diffusa treatment reduced the injury caused by Walker 256 tumor and maintained a metabolic balance. Our study demonstrated that this method provided new insights into metabolic alterations in tumor‐bearing biosystems and researching on the effects of H. diffusa on the endogenous metabolism in tumor‐bearing rats.