Apolipoprotein（apo） A-V is a novel member of the class of exchangeable apo＇s involved in triacylglycerol（TG）homeostasis.Whereas a portion of hepatic-derived apoA-V is secreted into plasma and functions to facilit...Apolipoprotein（apo） A-V is a novel member of the class of exchangeable apo＇s involved in triacylglycerol（TG）homeostasis.Whereas a portion of hepatic-derived apoA-V is secreted into plasma and functions to facilitate lipoprotein Iipase-mediated TG hydrolysis,another portion is recovered intracellularly,in association with cytosolic lipid droplets.Loss of apo A-V function is positively correlated with elevated plasma TG and increased risk of cardiovascular disease.Single nucleotide polymorphisms（SNP） in the APOA5 locus can affect transcription efficiency or introduce deleterious amino acid substitutions.Likewise,rare mutations in APOA5 that compromise functionality are associated with increased plasma TG and premature myocardial infarction.Genetically engineered mouse models and human population studies suggest that,in certain instances,supplementation with wild type（WT） apoA-V may have therapeutic benefit.It is hypothesized that individuals that manifest elevated plasma TG owing to deleterious APOA5 SNPs or rare mutations would respond to WT apoA-V supplementation with improved plasma TG clearance.On the other hand,subjects with hypertriglyceridemia of independent origin（unrelated to apoA-V function） may not respond to apoA-V augmentation in this manner.Improvement in the ability to identify individuals predicted to benefit,advances in gene transfer technology and the strong connection between HTG and heart disease,point to apoA-V supplementation as a viable disease prevention / therapeutic strategy.Candidates would include individuals that manifest chronic TG elevation,have low plasma apoA-V due to an APOA5 mutation/polymorphism and not have deleterious mutations/polymorphisms in other genes known to influence plasma TG levels.展开更多
An increasing amount of evidence indicates that there exists a pool of autoantibodies inthe serum of normal animals and humans. Characterized by low affinity andpolyreactivity, they are termed natural autoantibody, or...An increasing amount of evidence indicates that there exists a pool of autoantibodies inthe serum of normal animals and humans. Characterized by low affinity andpolyreactivity, they are termed natural autoantibody, or NAA, to be distinguishable frompathologically occurring autoantibodies. The existence and discovery of NAA render a chal-lenge to the traditionally accepted point of view that autoantibodies are harmful, and im-pose a new subject on modern immunology. The biogenesis and physiological展开更多
OBJECTIVE To investigate the effect of polyethylene imine glycol （PEI-PEG）/siRNA nanocomposites in the in vitro transfection of human gastric cancer SGC7901 cell lines and the down-regulation of gene expression of t...OBJECTIVE To investigate the effect of polyethylene imine glycol （PEI-PEG）/siRNA nanocomposites in the in vitro transfection of human gastric cancer SGC7901 cell lines and the down-regulation of gene expression of the adherence factor CD44v6. METHODS PEI-PEG/siRNA nanoparticles, in different N/P ratios, were synthesized and transfected into gastric cancer cells. Lipo2000/siRNA was used in the control group. The transfection efficiencies were observed under fluorescence microscope. The cytotoxicity of the nanoparticles was measured using the MTT assay （mononuclear cell direct cytotoxicity assay）, and the down-regulation effect of siRNA on CD44v6 gene was evaluated by Western blot. Based on the different N/P ratios, PEI-PEG/siRNA composites were synthesized and transfected into gastric cancer cells. Lipo2000/siRNA was used in the controls. The transfection efficiency was observed under fluorescence microscope. The cytotoxicity of the nanoparticles was measured using the MTT assay and the down-regulation effect of siRNA on CD44v6 gene was evaluated by Western blot. RESULTS After transfection, the transfection efficiency of the PEI-PEG/siRNA nanocomposites increased incrementally in N/P ratio value. The transfection efficiency improved with an increase in N/P ratio. When the N/P value was 15, fluorescence became more intense in the PEI-PEG/siRNA group than in the Lipo2000/siRNA group. At the same time, cell viability was （80.4 ± 5.6）% in the MTT reduction assay, which was similar to that in the Lipo2000/siRNA group. The results of Western blot analysis showed that the expression level of CD44v6 protein decreased to （59.7 ± 3.0）% after siRNA-CD44v6 was inhibited. CONCLUSION PEI-PEG could effectively form the nanocomposite in combination with siRNA, be transfected into the SGC7901 gastric cancer cell lines and inhibit CD44v6 protein expression. Moreover, as a genetic carrier, PEI-PEG copolymer has greater advantages, including high transfection e. ciency, less cytotoxicity and an easily alterable vector structure.展开更多
AIM: To investigate the clinical characteristics and genetic features of a Bietti crystalline dystrophy(BCD) proband in a Chinese family.METHODS: A Chinese female diagnosed with BCD complicated by bilateral choroidal ...AIM: To investigate the clinical characteristics and genetic features of a Bietti crystalline dystrophy(BCD) proband in a Chinese family.METHODS: A Chinese female diagnosed with BCD complicated by bilateral choroidal neovascularization(CNV) and her parents underwent complete ophthalmic examinations, including fundus autofluorescence(AF), fundus photography(FP), fundus fluorescein angiography(FFA), visual field testing, full-field electroretinography(ERG), optical coherence tomography(OCT) and optical coherence tomography angiography(OCTA). The sequencing of the CYP4 V2 gene was performed to the whole family.RESULTS: Bilateral tiny glittering crystal-like deposits and differing extent of atrophy of the retinal pigment epithelium(RPE) were found in the posterior pole of her fundus. The diffuse hypo-fluorescence shown on AF images and window defects shown on FFA both indicated the atrophy of the RPE and choriocapillaris. OCT showed the thinning of the RPE and choriocapillaris layer, ellipsoid zone(EZ) band defect and CNV in both eyes. OCTA images proofed bilateral type 2 CNV. The visual field test showed central and paracentral scotoma. ERG showed a slightly decreased b-wave in scotopic ERG. Gene sequencing identified three mutations of the CYP4 V2 gene, c.802_807 del, c.810 del T, and c.1388 G>A. The mutation c.1388 G>A was a novel substitution mutation.CONCLUSION: The novel mutation c.1388 G>A may be a possible cause that could induce the clinical phenotype of BCD.展开更多
4-（Methylnitrosamino）-1-（3-pyridyl）-1-butanone （NNK） is a potent and prevalent nitrosamine procarcinogen found in cigarette smoke. The aim of this work is to study alterations in peroxiredoxin （Prx） expression...4-（Methylnitrosamino）-1-（3-pyridyl）-1-butanone （NNK） is a potent and prevalent nitrosamine procarcinogen found in cigarette smoke. The aim of this work is to study alterations in peroxiredoxin （Prx） expression induced by NNK during carcinogenesis. Characterization of Prx genes from hamster was performed using bioinformatics.展开更多
基金Supported by a grant from NIH(R37-HL64159)an AHA Postdoctoral Fellowship Award(VS)
文摘Apolipoprotein（apo） A-V is a novel member of the class of exchangeable apo＇s involved in triacylglycerol（TG）homeostasis.Whereas a portion of hepatic-derived apoA-V is secreted into plasma and functions to facilitate lipoprotein Iipase-mediated TG hydrolysis,another portion is recovered intracellularly,in association with cytosolic lipid droplets.Loss of apo A-V function is positively correlated with elevated plasma TG and increased risk of cardiovascular disease.Single nucleotide polymorphisms（SNP） in the APOA5 locus can affect transcription efficiency or introduce deleterious amino acid substitutions.Likewise,rare mutations in APOA5 that compromise functionality are associated with increased plasma TG and premature myocardial infarction.Genetically engineered mouse models and human population studies suggest that,in certain instances,supplementation with wild type（WT） apoA-V may have therapeutic benefit.It is hypothesized that individuals that manifest elevated plasma TG owing to deleterious APOA5 SNPs or rare mutations would respond to WT apoA-V supplementation with improved plasma TG clearance.On the other hand,subjects with hypertriglyceridemia of independent origin（unrelated to apoA-V function） may not respond to apoA-V augmentation in this manner.Improvement in the ability to identify individuals predicted to benefit,advances in gene transfer technology and the strong connection between HTG and heart disease,point to apoA-V supplementation as a viable disease prevention / therapeutic strategy.Candidates would include individuals that manifest chronic TG elevation,have low plasma apoA-V due to an APOA5 mutation/polymorphism and not have deleterious mutations/polymorphisms in other genes known to influence plasma TG levels.
基金Project supported by Japan Sasagawa Scholarship for Medicine.
文摘An increasing amount of evidence indicates that there exists a pool of autoantibodies inthe serum of normal animals and humans. Characterized by low affinity andpolyreactivity, they are termed natural autoantibody, or NAA, to be distinguishable frompathologically occurring autoantibodies. The existence and discovery of NAA render a chal-lenge to the traditionally accepted point of view that autoantibodies are harmful, and im-pose a new subject on modern immunology. The biogenesis and physiological
基金This work was supported by the following funds： National Natural Science Foundation of China （No.30670951） Guangdong Provincial+5 种基金 Natural Science Foundation （No.06021322） Fund of Guangzhou Municipal Scientific Problem-Solving Program （No. 2003 Z 3-E0381） Fund of Guangdong Provincial Scientific Problem-Solving Program （No.2005 B31211002） Guangdong Provincial Government and Ministry of Education Project com- bining project initiation, study and research （No.2009B090300277）.
文摘OBJECTIVE To investigate the effect of polyethylene imine glycol （PEI-PEG）/siRNA nanocomposites in the in vitro transfection of human gastric cancer SGC7901 cell lines and the down-regulation of gene expression of the adherence factor CD44v6. METHODS PEI-PEG/siRNA nanoparticles, in different N/P ratios, were synthesized and transfected into gastric cancer cells. Lipo2000/siRNA was used in the control group. The transfection efficiencies were observed under fluorescence microscope. The cytotoxicity of the nanoparticles was measured using the MTT assay （mononuclear cell direct cytotoxicity assay）, and the down-regulation effect of siRNA on CD44v6 gene was evaluated by Western blot. Based on the different N/P ratios, PEI-PEG/siRNA composites were synthesized and transfected into gastric cancer cells. Lipo2000/siRNA was used in the controls. The transfection efficiency was observed under fluorescence microscope. The cytotoxicity of the nanoparticles was measured using the MTT assay and the down-regulation effect of siRNA on CD44v6 gene was evaluated by Western blot. RESULTS After transfection, the transfection efficiency of the PEI-PEG/siRNA nanocomposites increased incrementally in N/P ratio value. The transfection efficiency improved with an increase in N/P ratio. When the N/P value was 15, fluorescence became more intense in the PEI-PEG/siRNA group than in the Lipo2000/siRNA group. At the same time, cell viability was （80.4 ± 5.6）% in the MTT reduction assay, which was similar to that in the Lipo2000/siRNA group. The results of Western blot analysis showed that the expression level of CD44v6 protein decreased to （59.7 ± 3.0）% after siRNA-CD44v6 was inhibited. CONCLUSION PEI-PEG could effectively form the nanocomposite in combination with siRNA, be transfected into the SGC7901 gastric cancer cell lines and inhibit CD44v6 protein expression. Moreover, as a genetic carrier, PEI-PEG copolymer has greater advantages, including high transfection e. ciency, less cytotoxicity and an easily alterable vector structure.
基金Supported by National Key R&D Program of China(No.2020YFC2008200)Capital Clinical Diagnosis and Treatment Technology Research and Demonstration Application Project of China(No.Z191100006619029)。
文摘AIM: To investigate the clinical characteristics and genetic features of a Bietti crystalline dystrophy(BCD) proband in a Chinese family.METHODS: A Chinese female diagnosed with BCD complicated by bilateral choroidal neovascularization(CNV) and her parents underwent complete ophthalmic examinations, including fundus autofluorescence(AF), fundus photography(FP), fundus fluorescein angiography(FFA), visual field testing, full-field electroretinography(ERG), optical coherence tomography(OCT) and optical coherence tomography angiography(OCTA). The sequencing of the CYP4 V2 gene was performed to the whole family.RESULTS: Bilateral tiny glittering crystal-like deposits and differing extent of atrophy of the retinal pigment epithelium(RPE) were found in the posterior pole of her fundus. The diffuse hypo-fluorescence shown on AF images and window defects shown on FFA both indicated the atrophy of the RPE and choriocapillaris. OCT showed the thinning of the RPE and choriocapillaris layer, ellipsoid zone(EZ) band defect and CNV in both eyes. OCTA images proofed bilateral type 2 CNV. The visual field test showed central and paracentral scotoma. ERG showed a slightly decreased b-wave in scotopic ERG. Gene sequencing identified three mutations of the CYP4 V2 gene, c.802_807 del, c.810 del T, and c.1388 G>A. The mutation c.1388 G>A was a novel substitution mutation.CONCLUSION: The novel mutation c.1388 G>A may be a possible cause that could induce the clinical phenotype of BCD.
基金supported by Doctor Foundation of Zhengzhou University of Light IndustryScientific and technological research projects in Zhengzhou City(141PPTGG399)Scientific and technological research projects in Henan province
文摘4-（Methylnitrosamino）-1-（3-pyridyl）-1-butanone （NNK） is a potent and prevalent nitrosamine procarcinogen found in cigarette smoke. The aim of this work is to study alterations in peroxiredoxin （Prx） expression induced by NNK during carcinogenesis. Characterization of Prx genes from hamster was performed using bioinformatics.
