Biomedical subjects

Liguo Wang

Publications and source records attributed to Liguo Wang.

7 recordsLinked to original sources

PubMed2021

Genetic variants related to successful migraine prophylaxis with verapamil.

BACKGROUND: Currently, there is no biologically based rationale for drug selection in migraine prophylactic treatment. METHODS: To investigate the genetic variation underlying treatment response to verapamil prophylaxis, we selected 225 patients from a longitudinally established, deeply phenotyped migraine database (N = 5983), and collected uninterrupted quantitated verapamil treatment response data and DNA for these 225 cases. We recorded the number of headache days in the four weeks preceding treatment with verapamil and for four weeks, following completion of a treatment period with verapamil lasting at least five weeks. Whole-exome sequencing (WES) was applied to a discovery cohort consisting of 21 definitive responders and 14 definitive non-responders, and the identified single nucleotide polymorphisms (SNPs) showing significant association were genotyped in a separate confirmation cohort (185 verapamil treated patients). Statistical analysis of the WES data from the discovery cohort identified 524 SNPs associated with verapamil responsiveness (p < 0.01); among them, 39 SNPs were validated in the confirmatory cohort (n = 185) which included the full range of response to verapamil from highly responsive to not responsive. RESULTS: Fourteen SNPs were confirmed by both percentage and arithmetic statistical approaches. Pathway and protein network analysis implicated myo-inositol biosynthetic and phospholipase-C second messenger pathways in verapamil responsiveness, emphasizing the earlier pathogenic understanding of migraine. No association was found between genetic variation in verapamil metabolic enzymes and treatment response. CONCLUSION: Our findings demonstrate that genetic analysis in well-characterized subpopulations can yield important pharmacogenetic information pertaining to the mechanism of anti-migraine prophylactic medications.

Chemoprevention↗

PubMed2006

Using cryo-EM to measure the dipole potential of a lipid membrane.

The dipole potential of a lipid bilayer membrane accounts for its much larger permeability to anions than cations and affects the conformation and function of membrane proteins. The absolute value of the dipole potential has been very difficult to measure, although its value has been estimated to range from 200 to 1,000 mV from ion translocation rates, the surface potential of lipid monolayers, and molecular dynamics calculations. Here, a point charge probe method was used to investigate the dipole potentials of both ester and ether lipid membranes. The interactions between electrons and lipid molecules were recorded by phase-contrast imaging using cryo-EM. The magnitude and the profile of the dipole potential along the bilayer normal were obtained by subtracting the contribution of the atomic potential from the cryo-EM image intensity. The peak dipole potential was estimated to be 510 and 260 mV for diphytanoylphosphatidylcholine and diphytanylphosphatidylcholine, respectively.

Cryoelectron Microscopy↗

PubMed2006

Inhibition of CD147 expression reduces tumor cell invasion in human prostate cancer cell line via RNA interference.

CD147, also named extracelluar matrix metalloproteinase inducer (EMMPRIN), has been proved to be involved in the invasion and metastasis processes of tumor cells in many types of cancers. To determine the role of CD147 in the invasiveness properties of prostate cancer, we successfully downregulated CD147 by RNA interference (RNAi) technology, in PC-3 cell line at high level of CD147 expression. PC-3 cells were transfected with a pSilencer 4.1-CMV neo Vector coding for an RNA composed of two identical 19-nucleotide sequence motifs in an inverted orientation, separated by a 9-bp spacer to form a hairpin dsRNA capable of mediating target CD147 inhibition. Gelatin zymography was employed to determine the effect on reducing secretions of MMP-2 and MMP-9 of the transfected cells. Matrigel invasion assay was performed to evaluate the invasion ability of PC-3 cells in vitro. Our results showed that CD147 expression was significantly inhibited by small interfering RNAs (siRNA) transfectants in PC-3 cells at mRNA and protein levels, which resulted in dramatic reduction of invasion ability in tumor cells. Moreover, downregulation of CD147 resulted in reducing secretions of MMP-2, MMP-9. Taken together, CD147 downregulation by RNAi technology decreases the invasive capability of prostate cancer cells, demonstrating that stable expression of siRNA CD147 could potentially be an experimental approach for prostate cancer gene therapy.

Antigens, CD↗

PubMed2006

Cryo-EM and single particles.

Cryoelectronmicroscopy is a method for the imaging of macromolecules in the electron microscope. It was originally developed to determine membrane protein structures from two-dimensional crystals, but more recently "single-particle" techniques have become powerful and popular. Three-dimensional reconstructions are obtained from sets of single-particle images by extensive computer processing; the methods are being applied to many macromolecular assemblies.

Animals↗

PubMed2006

Transient reduction of PTI-1 expression by short interfering RNAs inhibits the growth of human prostate cancer cell lines.

The prostate tumor-inducing gene 1 (PTI-1) was originally identified by differential ribonucleic acid (RNA) display in human prostate carcinoma. PTI-1 is expressed in human prostate carcinoma but not in benign prostate hypertrophy or normal prostate tissue. PTI-1 may be a member of oncogenes that could affect protein translation and contribute to carcinoma development in human prostate. To investigate the role of PTI-1 in human prostate carcinoma, we constructed three different short interfering RNA (siRNA) vectors (pSilencer3.1-neo-Yu Lei [YL]1-2, -YL3-4 and -YL5-6), each of which was transfected into DU145 and PC3 human prostate cancer cell lines. Among these siRNAs, only pSilencer3.1-neo-YL1-2 could almost completely block the expression of PTI-1 in these two cell lines. The growth of the cell lines was then evaluated after transfection. The proliferation rate was retarded in DU145 and PC3 cells transfected with pSilencer3.1-neo-YL1-2, compared with the cells transfected with a control vector; namely, about 88.6% of DU145 and 80.2% of PC3 cancer cells were blocked at the G1 phase when transfected with pSilencer3.1-neo-YL1-2, compared to 62.0% in DU145 cells and 51.7% in PC3 cells, transfected with the control vector. Moreover, 68.3% of DU145 cells and 72.3% of PC3 cells were induced into apoptosis, while in control transfection, the population was 26.6% in DU145 cells and 28.4% in PC3 cells. These results indicate that blocking PTI-1 expression can inhibit the growth of certain prostate cancer cell lines. We suggest that PTI-1 may serve as a target for the gene-based therapy of human prostate carcinoma.

Adenocarcinoma↗

PubMed2005

The use of three-dimensional ultrasound micro-imaging to monitor prostate tumor development in a transgenic prostate cancer mouse model.

Longitudinal studies of mouse cancer models required large cohorts since autopsy was the only reliable method to evaluate treatment efficacy. This paper reports the use of high-resolution three-dimensional ultrasound micro-imaging to monitor prostate tumor development in genetically engineered mice. Twenty-nine genetically engineered prostate cancer mice, including castrated and uncastrated mice, were imaged by three-dimensional ultrasound. Qualitative comparisons of three-dimensional ultrasound images with histology sections of prostate tumors demonstrate the ability of ultrasound to accurately depict the size and shape of malignant masses in live mice. The correlation coefficient of tumor diameter measurements performed in vivo with three-dimensional ultrasound and at autopsy was 0.997. Prospective tumor detection sensitivity and specificity were 91.7% and 100%. Representative exponential growth curves constructed via longitudinal ultrasound imaging indicated diameter doubling times from 10 to 37 days for four prostate tumors during an initial period of rapid progression. Three-dimensional ultrasound will likely become the micro-imaging modality most readily adopted for mouse pre-clinical trial studies.

Animals↗

PubMed2005

[Dynamics of soil enzyme activity and nutrient content in intercropped cotton rhizosphere and non-rhizosphere].

The study with high yield cotton-wheat double cropping system showed that soil urease, invertase, protease and catalase activities in intercropped cotton field had the same changing trends with those in mono-cultured cotton field, but were significantly higher in intercropped than in mono-cultured cotton rhizosphere and non-rhizosphere at all development stages of cotton. During the intergrowth period of wheat and cotton, soil nutrient contents in intercropped cotton rhizosphere and non-rhizosphere were lower than or had little difference with those in mono-cultured cotton rhizosphere and non-rhizosphere, but became significantly higher after wheat harvested. The changing trends of soil nutrient contents in intercropped cotton field had little difference from those in mono-cultured cotton field, but the nutrient absorption peak appeared late. The soil enzyme activities and nutrient contents were generally higher in rhizosphere than in non-rhizosphere of both intercropped and mono-cultured cotton. Soil nutrient contents had significant (P < 0.05, n = 32) or very significant (P < 0.01, n = 32) correlation with the activities of soil urease, invertase and protease, but had little correlation with soil catalase activity.

Agriculture↗