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Biomedical subjects

Wei Geng

Publications and source records attributed to Wei Geng.

5 recordsLinked to original sources

High doses of bifendate elevate serum and hepatic triglyceride levels in rabbits and mice: animal models of acute hypertriglyceridemia.

AIM: To investigate the effects of bifendate on serum and hepatic lipids level in rabbits and mice. METHODS: Animals were administered bifendate [powdered pill suspended in 0.5% sodium carboxymethylcellulose (CMC)] at increasing doses (0.25-1 g/kg, ig). Blood lipid and apolipoprotein levels were measured using commercially available assay kits. RESULTS: The treatment of rabbits with a single dose of bifendate (0.3 g/kg) caused a time-dependent and biphasic change in serum triglyceride (TG) levels, with the value reaching a maximum (3-fold increase compared to the baseline value) between 24 and 36 h post-dosing. When mice were orally treated with bifendate (0.25-1 g/kg), serum TG levels increased by 39%-76% and 14%-39% at 24 and 48 h post-dosing, respectively. When given at daily doses of 0.25 and 1 g/kg for 4 d, bifendate increased serum TG levels (56%-79%), with concomitant elevations in apolipoprotein A-I and apolipoprotein B levels at 24 h after the last dosing. TG levels were also increased (11%-43%) in liver samples of mice receiving single or multiple doses of bifendate. However, bifendate treatment caused slight reductions in serum and hepatic total cholesterol levels (9%-13%). The hypertriglyceridemia induced by bifendate was ameliorated by fenofibrate but not inositol nicotinate treatment in mice. CONCLUSION: The findings suggest that bifendate treatment at high oral doses can cause an acute elevation in serum and hepatic TG levels.

Animals↗

[Ursolic acid induces apoptosis in colon cancer HT-29 cells].

OBJECTIVE: To study the antitumor effects of ursolic acid and mechanisms of its action. METHODS: The cells of human colorectal carcinoma cell line HT-29 were treated with ursolic acid at different concentration. The proliferation inhibition was examined by MTT assay. Morphological examination, TUNEL method and flow cytometry were used to detect apoptosis. Immunohistochemical method was used to detect the expression of apoptosis related genes caspase-9 and bcl-2. The semi-quantification of protein expression was analyzed by pathological image-analysis. RESULTS: UA inhibited the proliferation of HT-29 cells moderately. Apoptosis of HT-29 cells was induced by ursolic acid treatment. The morphology of HT-29 showed changes such as nuclear chromatin condensation and fragmentation. Sub-G(1) peak was found by flow cytometry. The maximal apoptosis rate was 11.63%. The expression of caspase-9 gene was enhanced. The expression of bcl-2 gene was decreased. All these effects were in a dose-dependent and time-depend manner. CONCLUSION: Apoptosis in colon cancer HT-29 cells is one of the key mechanisms of ursolic acid action and its antitumor activity may be applicable for the treatment of cancers.

Antineoplastic Agents, Phytogenic↗

Automatic tracking, feature extraction and classification of C elegans phenotypes.

This paper presents a method for automatic tracking of the head, tail, and entire body movement of the nematode Caenorhabditis elegans (C. elegans) using computer vision and digital image analysis techniques. The characteristics of the worm's movement, posture and texture information were extracted from a 5-min image sequence. A Random Forests classifier was then used to identify the worm type, and the features that best describe the data. A total of 1597 individual worm video sequences, representing wild type and 15 different mutant types, were analyzed. The average correct classification ratio, measured by out-of-bag (OOB) error rate, was 90.9%. The features that have most discrimination ability were also studied. The algorithm developed will be an essential part of a completely automated C. elegans tracking and identification system.

Algorithms↗

Quantitative classification and natural clustering of Caenorhabditis elegans behavioral phenotypes.

Genetic analysis of nervous system function relies on the rigorous description of behavioral phenotypes. However, standard methods for classifying the behavioral patterns of mutant Caenorhabditis elegans rely on human observation and are therefore subjective and imprecise. Here we describe the application of machine learning to quantitatively define and classify the behavioral patterns of C. elegans nervous system mutants. We have used an automated tracking and image processing system to obtain measurements of a wide range of morphological and behavioral features from recordings of representative mutant types. Using principal component analysis, we represented the behavioral patterns of eight mutant types as data clouds distributed in multidimensional feature space. Cluster analysis using the k-means algorithm made it possible to quantitatively assess the relative similarities between different behavioral phenotypes and to identify natural phenotypic clusters among the data. Since the patterns of phenotypic similarity identified in this study closely paralleled the functional similarities of the mutant gene products, the complex phenotypic signatures obtained from these image data appeared to represent an effective diagnostic of the mutants' underlying molecular defects.

Animals↗

Characterization of a CC49-based single-chain fragment-beta-lactamase fusion protein for antibody-directed enzyme prodrug therapy (ADEPT).

CC49 is a clinically validated antibody with specificity for TAG-72, a carbohydrate epitope that is overexpressed and exposed on the cell surface in a large fraction of solid malignancies. We constructed a single-chain fragment (scFv) based on CC49 and fused it to beta-lactamase (BLA). Following optimization of the scFv domain by combinatorial consensus mutagenesis (CCM) for increased expression and stability, we characterized the protein variant for binding, in vivo pharmacokinetics (PK), and antitumor efficacy. The fusion protein TAB2.5 possessed a similar binding specificity relative to the parent antibody CC49. TAB2.5 also showed prolonged retention (T(1/2) = 36.9 h) in tumor-bearing mice with tumor/plasma ratios of up to 1000. Preliminary evaluation of TAB2.5, in combination with a novel prodrug, GC-Mel, resulted in significant efficacy in a colorectal xenograft tumor model and supports the utility of the protein as an agent for tumor-selective prodrug activation.

Animals↗