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Biomedical subjects

Ying Chen

Publications and source records attributed to Ying Chen.

At least 181 records · Page 10Linked to original sources

Targeted expression of Cre recombinase to cone photoreceptors in transgenic mice.

PURPOSE: Disruption of widely expressed essential genes in mice often leads to embryonic or neonatal lethality. To circumvent this problem and dissect gene functions in the cone photoreceptors, we elected to generate cone photoreceptor specific cre transgenic mice. METHODS: Transgenic mice expressing Cre recombinase directed by the human red/green pigment (HRGP) gene promoter were generated. Candidate Cre-expressing lines were identified with RT-PCR. Cre-expressing mice were characterized with immunocytochemical assays and functional studies using a Cre activatable lacZ reporter mouse strain (R26R). Cone distribution was determined by immunohistochemistry and retinal function was measured by electroretinography (ERG) on six month old HRGP-cre mice. RESULTS: RT-PCR analysis suggested that several transgenic lines expressed cre mRNA in the retina. Beta-galactosidase staining on retinal flat mounts and sections from F1 mice derived from the HRGP-cre and R26R reporter mice suggested that two mouse strains were capable of carrying out efficient Cre mediated recombination in cone photoreceptors. Immunocytochemical staining of retinal sections demonstrated that Cre expression was localized to cone photoreceptors. Cone distribution and cone ERG analysis suggested that cone photoreceptors were normal in adult HRGP-cre mice. CONCLUSIONS: We have generated transgenic mice that efficiently express Cre recombinase in cone photoreceptor cells. The adult transgenic mice have normal cone distribution and function. They can be used in conditional knockout experiments for gene function studies in cone photoreceptors.

Animals↗

Anti-AIDS agents. Part 56: Synthesis and anti-HIV activity of 7-thia-di-O-(-)-camphanoyl-(+)-cis-khellactone (7-thia-DCK) analogs.

Two thia-DCK analogs (3a,b) were synthesized and evaluated for inhibition of HIV-1 replication in H9 lymphocytes. Compound 3a showed potent anti-HIV activity with an EC50 value of 0.14 microM and a therapeutic index of 1110. However, the corresponding 6-tert-butyl-substituted compound (3b) showed no suppression. The bioassay results indicated that thia-DCK analogs merit attention as potential HIV-1 inhibitors.

Anti-HIV Agents↗

Synthesis of meso-arylsulfanyl- and alkylsulfanyl-substituted porphyrins via palladium-mediated C-S bond formation.

A family of new meso-arylsulfanyl- and alkylsulfanyl-substituted porphyrins were efficiently synthesized from direct reactions of meso-brominated porphyrins with thiols via palladium-mediated C-S bond formation. The catalytic method can be performed under mild conditions with both mono- and bis-substituted meso-bromoporphyrins as well as their zinc complexes and is suitable for different types of thiols. With the use of selenols, meso-seleno-substituted porphyrins can also be prepared similarly.

Catalysis↗

Some unreported by-products from the reaction of 1,4-dien-3-one steroids with 2-(methylammo)benzethiol/BF3.

In a previous report, it was demonstrated that the 3-carbonyl of androsta-1,4-dien-3,17-dione (ADD) can be selectively protected with 2-(methylamino)benzethiol in the presence of BF3 in good yield. We explored the applicability of this method for other 1,4-dien-3-one steroids and got the desired protective products in different yield. Other than the usual protected products, we also got some unexpected by-products, including benzathiazol[4,3-b]-estra steroids. Their structures were determined by spectral analysis.

Boranes↗

Anti-AIDS agents. Part 62: anti-HIV activity of 2'-substituted 4-methyl-3',4'-di-O-(-)-camphanoyl-(+)-cis-khellactone (4-methyl DCK) analogs.

Four 4-methyl-3',4'-di-O-(-)-camphanoyl-(+)-cis-khellactone (4-methyl DCK) analogs (7a-d) with different alkyl substituents at the 2'-position were synthesized and evaluated for inhibition of HIV-1 replication in H9 lymphocytes. 2'-Methyl-2'-ethyl-4-methyl DCK (7b) was more potent (EC(50)=0.22 microM, TI>175) than the other three compounds (7a, 7c, and 7d), but significantly less potent than 4-methyl DCK (2, EC(50)=0.0059 microM, TI>6600). The bioassay results indicated that the 2'-substituents had a strong effect on the anti-HIV activity, and gem-dimethyl substitution at the 2'-position was greatly preferable to larger alkyl substituents or hydrogen atoms.

Anti-HIV Agents↗

Bromoporphyrins as versatile synthons for modular construction of chiral porphyrins: cobalt-catalyzed highly enantioselective and diastereoselective cyclopropanation.

5,10-Bis(2',6'-dibromophenyl)porphyrins bearing various substituents at the 10 and 20 positions were demonstrated to be versatile synthons for modular construction of chiral porphyrins via palladium-catalyzed amidation reactions with chiral amides. The quadruple carbon-nitrogen bond formation reactions were accomplished in high yields with different chiral amide building blocks under mild conditions, forming a family of D2-symmetric chiral porphyrins. Cobalt(II) complexes of these chiral porphyrins were prepared in high yields and shown to be active catalysts for highly enantioselective and diastereoselective cyclopropanation under a practical one-pot protocol (alkenes as limiting reagents and no slow addition of diazo reagents).

Journal Article↗

Genetically altered mice to evaluate glutathione homeostasis in health and disease.

The tripeptide glutathione (GSH) is part of an integrated antioxidant system that protects cells and tissues from oxidative damage. Oxidative stress can result from exposure to excessive amounts of endogenous and exogenous electrophiles. Until recently, animal and cell model systems used to investigate the role of GSH in disease processes had employed chemical agents that deplete cellular GSH by inhibiting GSH synthesis or by reacting chemically with GSH. Such models have proven useful, but questions concerning nonspecific effects of such chemicals remain. Recently, our laboratories and others have developed mouse models with genetic deficiencies in enzymes of the GSH biosynthetic pathway. This review focuses on the regulation of GSH homeostasis and, specifically, the new GSH-deficient mouse models that have been developed. These models will improve our understanding of the role of GSH in animal and human diseases.

Animals↗

Pathobiological significance of vascular endothelial growth factor and Maspin expressions in human gastric carcinoma.

AIM: To investigate the correlation between expression of vascular endothelial growth factor (VEGF) and cell differentiation, invasion, metastasis and Maspin expression in gastric carcinoma. METHODS: Formalin-fixed paraffin-embedded tissue specimens from 73 cases of gastric carcinoma were studied with SP immunohistochemistry, using anti-VEGF monoclonal antibody, and thirty-nine of them were studied using anti-Maspin monoclonal antibody. VEGF expression was compared with the clinical stage, lymph node metastasis, and Borrmann's and WHO's classification of gastric carcinoma. RESULTS: The positive rate of VEGF expression was significantly higher in adjacent non-carcinoma epithelia (ANCE) than in non-metaplastic, non-carcinoma gastric epithelia (NMNCE), which were at least 4 cm distant from the primary tumor (P = 0.000, chi2 = 73.03). The positive rate of VEGF expression was significantly higher in advanced gastric carcinoma (AGC) than in early gastric carcinoma (EGC) (P = 0.032, chi2 = 4.62). The positive rate of VEGF expression in gastric carcinomas with lymph node metastases was significantly higher than that in those without metastasis (P = 0.006, chi2 = 7.47). Maspin was weakly expressed in 16 out of 39 cases of NMNCE, and the positive immunoreaction was limited to gland cells of the stomach body. There was no significant correlation between the expression of VEGF and histological or gross classifications, and correlation between the expressions of VEGF and Maspin in gastric carcinoma (P = 0.648, chi2 = 0.21). CONCLUSION: Expression of VEGF is significantly correlated to the malignant biological behaviors of gastric carcinoma, but there is no significant correlation between the expression of VEGF and Maspin.

Adenocarcinoma, Mucinous↗

Anti-cancer effects of COX-2 inhibitors and their correlation with angiogenesis and invasion in gastric cancer.

AIM: To observe the anti-cancer effects of COX-2 inhibitors and investigate the relationship between COX-2 inhibitors and angiogenesis, infiltration or metastasis in SGC7901 cancer xenografts. METHODS: Thirty athymic mice xenograft models with human stomach cancer cell SGC7901 were established and divided randomly into 3 groups of 10 each. Sulindac, one non-specific COX inhibitor belonging to non-steroidal anti-inflammatory drugs (a series of COX inhibitors known as NSAIDs) and celecoxib, one selective COX-2 inhibitor (known as SCIs) were orally administered to mice of treatment groups. Immunohistochemistry was used to examine the expression of PCNA, CD44v6 and microvessel density (MVD). Apoptosis was detected by using TUNEL assay. RESULTS: Tumors in sulindac and celecoxib groups were significantly smaller than those in control group from the second week after drug administration (P<0.01). In treatment group, the cell proliferation index was lower (P<0.05) and apoptosis index was higher (P<0.05) than those in control groups. Compared with the controls, microvessel density was reduced (P<0.01) and expression of CD44v6 on tumor cells was weakened (P<0.05) in treatment groups. CONCLUSION: COX-2 inhibitors have anticancer effects on gastric cancer. They play important roles in angiogenesis and infiltration or metastasis of stomach carcinoma. The anticancer effects of COX-2 inhibitors may include inducing apoptosis, suppressing proliferation, reducing angiogenesis and weakening invasiveness.

Animals↗

Anti-AIDS agents. Part 58: synthesis and anti-HIV activity of 1-thia-di-O-(-)-camphanoyl-(+)-cis-khellactone (1-thia-DCK) analogues.

Two 1-thia-DCK analogues (9a and 9b) were synthesized and evaluated for inhibition of HIV-1 replication in H9 lymphocytes. Compound 9a showed excellent anti-HIV activity with an EC(50) value of 0.00012 microM and therapeutic index of 1408000. Compound 9b was less active with EC(50) and TI values of 3.11 microM and 62.3, respectively. The bioassay results indicated that thia-DCK analogues merit attention as potential HIV-1 inhibitors.

Anti-HIV Agents↗

Surface properties of bamboo fiber and a comparison with cotton linter fibers.

In order to understand the different touch senses from bamboo and cotton fibers, the surface properties of bamboo fiber, e.g., the surface free energy, the Lifshitz-van der Waals force, and Lewis acid and base components have been determined using the column wicking technique. Taking the traditional cotton linter fiber as a reference, this paper shows that both these fibers have the similar surface free energies. However, a big difference between these two fibers which has been importantly observed is that the bamboo fiber having greater Lewis acid component seems to be double than the cotton linter fiber. Since water has been found to have such surface property, it is suggested that the bamboo fiber touch in the skin of people may like the touch between water and skin of people. Meanwhile, other surface properties of these two fibers are compared.

Acid-Base Equilibrium↗

General synthesis of meso-amidoporphyrins via palladium-catalyzed amidation.

A series of meso-amidoporphyrins were facilely synthesized by direct reactions of meso-brominated porphyrins with amides via palladium-catalyzed amidation reaction. Using a combination of palladium precursor Pd(OAc)(2) or Pd(2)(dba)(3) and phosphine ligand Xantphos, both 5-bromo-10,20-diphenylporphyrin and 5,15-dibromo-10,20-diphenylporphyrin, as well as their zinc complexes, can be effectively coupled with a wide variety of amides to give the corresponding mono- and bis-substituted meso-amidoporphyrins in high yields under mild conditions. [reaction: see text]

Amides↗

Vitamin B12 derivatives as natural asymmetric catalysts: enantioselective cyclopropanation of alkenes.

Vitamin B(12) derivatives were found for the first time to be general and efficient catalysts for asymmetric cyclopropanation of alkenes with ethyl diazoacetate (EDA). Among several common derivatives, aquocobalamin (B(12a)) was shown to be the most effective catalyst for a variety of alkenes, providing cis-dominant cyclopropanes in excellent yields and moderate enantioselectivity. Reactivity studies under different conditions suggest that the active species in the proposed catalytic cycle is the base-on cob(II)alamin (B(12r)) that is generated possibly via in situ reduction of B(12a) by EDA.

Alkenes↗

Constitutive cardiac overexpression of sarcoplasmic/endoplasmic reticulum Ca2+-ATPase delays myocardial failure after myocardial infarction in rats at a cost of increased acute arrhythmias.

BACKGROUND: Heart failure often complicates myocardial infarction (MI), and sarcoplasmic/endoplasmic reticulum Ca2+-ATPase (SERCA2a) is underexpressed in the failing myocardium. We examined the effect of preexisting cardiac SERCA2a protein overexpression on rat survival and left ventricular (LV) remodeling after MI. METHODS AND RESULTS: Baseline myocardial SERCA2a expression was 37% higher in transgenic (TG) rats than in their wild-type (WT) controls, consistent with enhanced myocardial function. The mortality rate of TG rats during the 24 hours after surgical MI was higher than that of WT rats (71% versus 35%, P<0.001), associated with a higher frequency of ventricular arrhythmias, and was normalized by lidocaine treatment. The increased acute-phase mortality in TG rats was not accompanied by increased 6-month mortality. Function of the noninfarcted myocardium, as assessed by tissue Doppler imaging, was higher in TG rats than in WT rats for up to 1 month after MI, a beneficial effect no longer observed at 3 months. LV remodeling and global function were similar in TG and WT rats. No difference in papillary muscle function was found at 6 months. CONCLUSIONS: Constitutive cardiac SERCA2a overexpression has a transient beneficial effect on remote myocardium function in rat MI, with no improvement in LV global function or prevention of LV remodeling and failure. This benefit is associated with a higher risk of acute mortality, which is prevented by lidocaine treatment.

Acute Disease↗

Identification of human Clock gene variants by denaturing high-performance liquid chromatography.

The human Clock gene ( hClock) encodes the CLOCK protein essential for the function of the circadian system. We have screened the entire coding region, including the 5' and 3' untranslated regions (UTRs) and the flanking intronic regions, of the hClock gene for sequence variations in 70 unrelated Chinese Singaporeans with denaturing high-performance liquid chromatography (dHPLC). A total of 15 sequence variations were detected, five of which were novel. All involved single base changes. There were 12 substitutions and three insertions/deletions. All except one were found in the introns or the UTRs. Frequencies of the minor allele for all 15 polymorphisms ranged from 0.7% to almost 50%. For the eight sites whose minor allele frequency was found to be at least 10%, pair-wise comparisons revealed that all except one were in almost complete linkage disequilibrium. Our identification of additional single nucleotide polymorphisms in the hClock gene would provide markers whose frequencies could be established in the selected population and used for further analysis of the phenotypic effects. Our results would also be useful for better planning in the selection of polymorphisms for future genetic association studies involving the hClock gene.

CLOCK Proteins↗

Hybrid event based control architecture for tele-robotic systems controlled through Internet.

A new hybrid event based control architecture for tele-robotic systems controlled through the Internet is proposed in this paper. Different from the traditional event based control method, the new framework does not require every part of the system to be strictly event synchronized. Instead, it allows time referenced control components to be integrated into this framework, which makes it more convenient to develop Internet based control systems. Since there are two reference variables, time and event, in this architecture, how to coordinate these components with different references to keep the stability of the whole system is discussed in detail in this paper. To verify this new idea, an experiment was conducted to control the end effector of a PUMA robot tracking a continuous state trajectory given on-line by the remote operator. Experimental results confirmed the stability of such systems being controlled through the Internet in real-time.

Algorithms↗

Lasonolides C-g, five new lasonolide compounds from the sponge Forcepia sp.

Five new marine-derived macrolide compounds, lasonolides C (3), D (4), E (5), F (6), and G (7), have been isolated from the sponge Forcepia sp. along with the parent compound in the series, lasonolide A (1). Their structures were elucidated on the basis of spectral data. Compounds 3-5 inhibit the in vitro proliferation of A-549 human lung adenocarcinoma cells with IC50's of 0.13, 4.5, and 0.31 microM, respectively. Compounds 3-6 inhibit the in vitro proliferation of PANC-1 human pancreatic carcinoma cells with IC50's of 0.38, 4.89, 0.57, and 15.6 microM, respectively. Compound 3 inhibits the in vitro proliferation of the NCI-ADR-RES cell line with an IC50 of 1.12 microM.

Animals↗