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Biomedical subjects

Yang Wang

Publications and source records attributed to Yang Wang.

241 records · Page 14Linked to original sources

Bimodal effect of hypoxia in cancer: role of hypoxia inducible factor in apoptosis.

The effects of the separate and combined application of hypoxia and antisense oligonucleotides (ASO) against hypoxia inducible factor 1alpha (HIF1A) on cancer cells were examined. Experiments were carried out on human ovarian carcinoma cells in four series: (1) control [Normoxia (5% CO2 in air), no treatment], (2) hypoxia (1% O2, 5% CO2, and 94% N2 for 48 h), (3) treatment with ASO targeted to HIF1A (48 h), and (4) combined action of hypoxia and ASO. After treatment, the following processes and factors were monitored: apoptosis, cellular metabolism and viability, expression of genes encoding HIF1A, von Hippel-Lindau tumor suppressor protein (VHL), and genes responsible for cell death induction and antiapoptotic defense (P53, BCL2, BAX, and caspases 9 and 3). Expression of caspase 9 and HIF1A protein was confirmed by Western blotting. Liposomes were used as a delivery system of HIF1A ASO. It was found that hypoxia alone significantly disturbed cellular metabolism, reducing the level of respiration by 50% when compared with control. Hypoxia induced apoptosis by upregulating the P53-, BAX-, and caspase-dependent cell death pathways, while activating cellular antiapoptotic defense by the overexpression of BCL2 protein. Both opposing effects were dependent on the overexpression of hypoxia inducible factor. We conclude that hypoxia induces a bimodal effect, simultaneously promoting cell death and activating cellular resistance. The downregulation of HIF1A promoted cell death induction and prevented activation of cellular defense by hypoxia. This suggests that HIF1A is a potential candidate for anticancer therapeutic targeting.

Apoptosis↗

JNK1 as a molecular target to limit cellular mortality under hypoxia.

Many pathological conditions and environmental impacts lead to a decrease in tissue oxygen supply and severe cellular hypoxia. This secondary hypoxia can disturb cellular homeostasis, limiting the efficacy of the prescribed treatment for the primary lesion, eventually leading to cellular and organismal death. Jun N-terminal kinase 1 (JNK1) plays a major role in the hypoxic cellular damage. Therefore, we hypothesized that suppression of JNK1 activity will decrease cellular mortality under hypoxia and might increase the efficacy of traditional treatment of many pathological conditions. These investigations are aimed at studying the influence of the suppression of JNK1 activity on the development of cellular hypoxic damage. We used antisense oligonucleotides (ASO) and small interfering RNA (siRNA) targeted to JNK1 mRNA to inhibit the protein synthesis. Experiments were carried out on a cell culture under normoxia and hypoxic conditions that led to the death of approximately 50% of cells. ASO or siRNA was delivered by neutral or cationic liposomes. Intracellular localization of ASO and liposomes and mechanisms of apoptosis were studied. We found that the suppression of JNK1 activity by liposomal antisense oligonucleotides or siRNA limits the caspase-dependent apoptosis signaling pathway and decreases cellular mortality after severe hypoxia. JNK1 protein might be an attractive target for antihypoxic therapy in increasing resistance to many pathological conditions and diseases, leading to the oxygen deficit.

Apoptosis↗

In situ evading of phagocytic uptake of stealth solid lipid nanoparticles by mouse peritoneal macrophages.

Stealth solid lipid nanoparticles (SSLN) were prepared and evaluated for the effect of evading phagocytic uptake by mouse peritoneal macrophages in situ. Fluorescent SSLNs were prepared by emulsion/evaporation with rhodamine B as the fluorescent marker and polyoxyethylene stearate as stealth agent in a stearic acid matrix. Macrophages were induced chemically through intraperitoneally injecting 1% sodium thioglycolate. After 4 days of cultivation, SSLNs suspension was injected intraperitoneally and phagocytosis taken out in situ. At definite time intervals, peritoneal fluid was drawn out and analyzed by flow cytometer. Maximum uptake by macrophages was observed at 2 hr after injection of nanoparticles. At all time intervals, phagocytic uptake of Solid lipid nanoparticles (SLNs) was better than SSLNs. Longer and dense polyethylene glycol chains led to reduced uptake by macrophages. Both SSLNs and SLN had uptake by macrophages to some extent, and the in situ model was suitable for evaluating interactions between cells and nanoparticles.

Animals↗

Preparation of 6-thioguanosine phosphoramidite for oligoribonucleotide synthesis.

6-Thioguanosine phosphoramidite was prepared, using 2,4-dinitrophenyl as protection group for thio-function, and its stability towards conditions of RNA synthesis was investigated. The results show that the monomer was stable under the conditions of RNA synthesis and suitable for incorporation of thioguanine into oligoribonucleotides.

Amides↗

Clinical application of microskin grafting to repair granulation or decrustation wounds.

One hundred seven granulating or decrustation wounds in 58 patients were grafted with microskin grafts of different sizes. The modified procedure has been used successfully for different wound sites, such as limb, chest, abdomen, and the back, with satisfactory results. Signs of epithelialization were shown within 5 to 22 days in 40 patients. The wound healing rate was 94.4%, including 71.9% total healing rate and 22.4% improved healing rate. We think that this method could be applied to either granulation or decrustation wounds in addition to excision wounds.

Adolescent↗

Media violence exposure and frontal lobe activation measured by functional magnetic resonance imaging in aggressive and nonaggressive adolescents.

OBJECTIVE: To understand better the relation between media violence exposure, brain functioning, and trait aggression, this study investigated the association between media violence exposure and brain activation as measured by functional magnetic resonance imaging (fMRI) in groups of normal adolescents and adolescents with disruptive behavior disorder (DBD) with aggressive features. METHODS: Seventy-one participants underwent neuropsychologic evaluation and assessment of exposure to violent media. Subjects also were evaluated with fMRI while performing a counting Stroop (CS) task. RESULTS: Frontal lobe activation was reduced in aggressive subjects compared with control subjects. In addition, differences in frontal lobe activation were associated with differences in media violence exposure. Specifically, activation during performance of the CS in control subjects with high media violence exposure resembled that seen in DBD subjects. CONCLUSIONS: Our findings suggest that media violence exposure may be associated with alterations in brain functioning whether or not trait aggression is present.

Adolescent↗

Attribute clustering for grouping, selection, and classification of gene expression data.

This paper presents an attribute clustering method which is able to group genes based on their interdependence so as to mine meaningful patterns from the gene expression data. It can be used for gene grouping, selection, and classification. The partitioning of a relational table into attribute subgroups allows a small number of attributes within or across the groups to be selected for analysis. By clustering attributes, the search dimension of a data mining algorithm is reduced. The reduction of search dimension is especially important to data mining in gene expression data because such data typically consist of a huge number of genes (attributes) and a small number of gene expression profiles (tuples). Most data mining algorithms are typically developed and optimized to scale to the number of tuples instead of the number of attributes. The situation becomes even worse when the number of attributes overwhelms the number of tuples, in which case, the likelihood of reporting patterns that are actually irrelevant due to chances becomes rather high. It is for the aforementioned reasons that gene grouping and selection are important preprocessing steps for many data mining algorithms to be effective when applied to gene expression data. This paper defines the problem of attribute clustering and introduces a methodology to solving it. Our proposed method groups interdependent attributes into clusters by optimizing a criterion function derived from an information measure that reflects the interdependence between attributes. By applying our algorithm to gene expression data, meaningful clusters of genes are discovered. The grouping of genes based on attribute interdependence within group helps to capture different aspects of gene association patterns in each group. Significant genes selected from each group then contain useful information for gene expression classification and identification. To evaluate the performance of the proposed approach, we applied it to two well-known gene expression data sets and compared our results with those obtained by other methods. Our experiments show that the proposed method is able to find the meaningful clusters of genes. By selecting a subset of genes which have high multiple-interdependence with others within clusters, significant classification information can be obtained. Thus, a small pool of selected genes can be used to build classifiers with very high classification rate. From the pool, gene expressions of different categories can be identified.

Algorithms↗