Efficacy evaluation of serum galectin-3 in hypertension complicated with diastolic dysfunction.

Serum galectin-3 (Gal-3) in patients with hypertension complicated with diastolic dysfunction and its predictive value for efficacy were investigated. One hundred patients with hypertension complicated with diastolic dysfunction admitted to the First Affiliated Hospital of Jiamusi University from June 2017 to December 2018 were enrolled as group A, symptomatically treated with conventional drugs. Further 80 individuals undergoing physical examination during the same period were enrolled as group B. Patients in the two groups were subjected to echocardiography to observe mitral valve early peak flow velocity (EPFV), atrial peak flow velocity (APFV), maximum flow velocity ratio of early to atrial diastole (EPFV/APFV) and peak mitral annulus velocity (E/E'). Enzyme-linked immunosorbent assay (ELISA) was used to detect serum Gal-3 concentration. According to efficacy after treatment, patients in group A were divided into the effective group (71 patients) and the invalid group (29 patients). Gal-3 concentration in group A was significantly higher than that in group B (P<0.05). After treatment, the concentration in group A was significantly lower than that before treatment (P<0.05), but significantly higher than that in group B (P<0.05). Gal-3 concentration was significantly higher in patients with cardiac function grades II, III and IV than that in patients with grade I (P<0.05). According to Spearman's test, Gal-3 concentration was positively correlated with cardiac function grading (r=0.569, P<0.001). Compared with before treatment in group A, patients after treatment had significantly higher EPFV and EPFV/APFV (P<0.05), but significantly lower APFV and E/E' (P<0.05). Before treatment, Gal-3 concentration in the effective group was significantly lower than that in the invalid group (P<0.05). According to the receiver operating characteristic (ROC) curve, the area under curve (AUC) of Gal-3 concentration for evaluating efficacy was 0.792, the sensitivity was 73.24%, and the specificity was 79.31%. In conclusion, Gal-3 may be involved in the development and progression of hypertension complicated with diastolic dysfunction. Its concentration increases with the rise of cardiac function grading but significantly decreases after treatment. Therefore, Gal-3 concentration before treatment can be used as a potential predictor of efficacy.

Profiling of differentially expressed microRNAs in arrhythmogenic right ventricular cardiomyopathy.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a kind of primary cardiomyopathy characterized by the fibro-fatty replacement of right ventricular myocardium. Currently, myocardial microRNAs have been reported to play critical role in the pathophysiology of cardiovascular pathophysiology. So far, the profiling of microRNAs in ARVC has not been described. In this study, we applied S-Poly (T) Plus method to investigate the expression profile of microRNAs in 24 ARVC patients heart samples. The tissue levels of 1078 human microRNAs were assessed and were compared with levels in a group of 24 healthy controls. Analysis of the area under the receiver operating characteristic curve (ROC) supported the 21 validated microRNAs to be miRNA signatures of ARVC, eleven microRNAs were significantly increased in ARVC heart tissues and ten microRNAs were significantly decreased. After functional enrichment analysis, miR-21-5p and miR-135b were correlated with Wnt and Hippo pathway, which might involve in the molecular pathophysiology of ARVC. Overall, our data suggested that myocardial microRNAs were involved in the pathophysiology of ARVC, miR-21-5p and miR-135b were significantly associated with both the myocardium adipose and fibrosis, which was a potential disease pathway for ARVC and might to be useful as therapeutic targets for ARVC.

Metabolomics coupled with proteomics advancing drug discovery toward more agile development of targeted combination therapies.

To enhance the therapeutic efficacy and reduce the adverse effects of traditional Chinese medicine, practitioners often prescribe combinations of plant species and/or minerals, called formulae. Unfortunately, the working mechanisms of most of these compounds are difficult to determine and thus remain unknown. In an attempt to address the benefits of formulae based on current biomedical approaches, we analyzed the components of Yinchenhao Tang, a classical formula that has been shown to be clinically effective for treating hepatic injury syndrome. The three principal components of Yinchenhao Tang are Artemisia annua L., Gardenia jasminoids Ellis, and Rheum Palmatum L., whose major active ingredients are 6,7-dimethylesculetin (D), geniposide (G), and rhein (R), respectively. To determine the mechanisms underlying the efficacy of this formula, we conducted a systematic analysis of the therapeutic effects of the DGR compound using immunohistochemistry, biochemistry, metabolomics, and proteomics. Here, we report that the DGR combination exerts a more robust therapeutic effect than any one or two of the three individual compounds by hitting multiple targets in a rat model of hepatic injury. Thus, DGR synergistically causes intensified dynamic changes in metabolic biomarkers, regulates molecular networks through target proteins, has a synergistic/additive effect, and activates both intrinsic and extrinsic pathways.

Pharmacokinetics of hesperetin and naringenin in the Zhi Zhu Wan, a traditional Chinese medicinal formulae, and its pharmacodynamics study.

Zhi Zhu Wan (ZZW), a classical Chinese medical formulae consisted of Atractylodes Rhizome and Fructus Citrus Immaturus, has been commonly used for treatment of gastrointestinal diseases. Hesperetin and naringenin are the main components of ZZW, and both can alleviate intestinal tract disorders. In this work, plasma pharmacokinetics and pharmacodynamics characteristics of ZZW after oral administration were investigated using a rapid and sensitive ultra performance liquid chromatography-tandem mass spectrometry method with an electrospray ionization source in positive ion mode. Biosamples were prepared using methanolic precipitation, and the separation of hesperetin and naringenin was achieved on a Waters ACQUITY HSS BEH (2.1 mm × 5 mm, 1.7 µm) column by linear gradient elution, and the total run time was only 3 min. Data were analyzed and estimated using WinNonlin Professional version 5.1. With pharmacokinetic analysis, the estimated pharmacokinetic parameters (i.e. C(max), area under the concentration-time curve (AUC) and t(1/2)), were C(max) = 776.06 ng/mL, AUC = 9473 ng/mL·h, t1/2 = 5.26 h for hesperetin and C(max) = 2910.6 ng/mL, AUC = 40607.9 ng/mL·h, t1/2 = 4.69 h for naringenin, respectively. In the present study, we have also valuated and clarified the effect of ZZW on small intestinal movement. It was found that ZZW can accelerate intestinal motility in mice and may hold a promising treatment for intestinal diseases.

Rho-associated coiled kinase inhibitor Y-27632 promotes neuronal-like differentiation of adult human adipose tissue-derived stem cells.

BACKGROUND: Y-27632 is a specific inhibitor of Rho-associated coiled kinase (ROCK) and has been shown to promote the survival and induce the differentiation of a variety of cells types. However, the effects of Y-27632 on adult human adipose tissue-derived stem cells (ADSCs) are unclear. This study aimed to investigate the effects of Y-27632 on the neuronal-like differentiation of ADSCs. METHODS: ADSCs were isolated from women undergoing plastic surgery and cultured. ADSCs were treated with different doses of Y-27632 and observed morphological changes under microscope. The expression of nestin, neuron specific enolase (NSE) and microtubule-associated protein-2 (MAP-2) in ADSCs treated with Y-27632 was detected by immunocytochemistry and Western blotting analysis. RESULTS: Y-27632 had the potency to induce neuronal-like differentiation in ADSCs in a dose-dependent manner. Moreover, the differentiation induced by Y-27632 was recovered upon drug withdraw. ADSCs treated with Y-27632 expressed neuronal markers such as NSE, MAP-2 and nestin while untreated ADSCs did not express these markers. CONCLUSION: Selective ROCK inhibitor Y-27632 could potentiate the neuronal-like differentiation of ADSCs, suggesting that Y-27632 could be utilized to induce the differentiation of ADSCs to neurons and facilitate the clinical application of ADSCs in tissue engineering.

Urine metabolomics analysis for biomarker discovery and detection of jaundice syndrome in patients with liver disease.

Metabolomics is a powerful new technology that allows for the assessment of global metabolic profiles in easily accessible biofluids and biomarker discovery in order to distinguish between diseased and nondiseased status information. Deciphering the molecular networks that distinguish diseases may lead to the identification of critical biomarkers for disease aggressiveness. However, current diagnostic methods cannot predict typical Jaundice syndrome (JS) in patients with liver disease and little is known about the global metabolomic alterations that characterize JS progression. Emerging metabolomics provides a powerful platform for discovering novel biomarkers and biochemical pathways to improve diagnostic, prognostication, and therapy. Therefore, the aim of this study is to find the potential biomarkers from JS disease by using a nontarget metabolomics method, and test their usefulness in human JS diagnosis. Multivariate data analysis methods were utilized to identify the potential biomarkers. Interestingly, 44 marker metabolites contributing to the complete separation of JS from matched healthy controls were identified. Metabolic pathways (Impact-value≥0.10) including alanine, aspartate, and glutamate metabolism and synthesis and degradation of ketone bodies were found to be disturbed in JS patients. This study demonstrates the possibilities of metabolomics as a diagnostic tool in diseases and provides new insight into pathophysiologic mechanisms.

Rapid and global detection and characterization of the constituents in ShengMai San by ultra-performance liquid chromatography-high-definition mass spectrometry.

An ultra-performance liquid chromatography-high definition mass spectrometry (UPLC-HDMS) method was developed for detection and characterization of the chemical constituents in ShengMai San (SMS), a traditional Chinese medical formula (TCMF). The full-scan LC-MS/MS data sets combined with extra mass were acquired within 14 min using UPLC-HDMS in the MS(E) mode in a single injection. As a result, 92 compounds were identified by comparing the accurate mass and fragments information with that of the authentic standards as well as by MS analysis and the correlative references data. These constituents included ginsenosides, lignans, steroidal saponins and homoisoflavanones. Among them, 25-hydroxyginsenosides were discovered in SMS for the first time. Compare with the previous studies, our research detected more compounds and presented more rapid by applying UPLC-HDMS. It is concluded that a rapid and effective method has been established based on UPLC-HDMS with the utilization of MS(E) , which shows high sensitivity and resolution that is suitable for identifying the constituents of SMS, and this method could be applied to other TCMF.