Peroxisome proliferator-activated receptors (PPARs)are ligand-activated nuclear tran-scription factors,playing an important role in the regulation of glucose and lipids metabolism,inflamma-tion response,proliferation and differentiation.Some drugs targeted on PPARs,such as lipid-lowering and antidiabetic drugs have been developed.Some PPAR agonists were found carcinogenic in animal experi ments,including PPAR αagonist fibrates,PPARγagonist thiazolidinediones,PPARα/γdual ago-nist compounds,and PPARδagonist compounds for clinical development.PPARαagonist carcinogenicity is associated with PPAR receptor activation that regulates lipid metabolis m,and leads to lipids abnormali-ties and increase by peroxisome oxidase in reactive oxygen species (ROS),causing DNA damage. Kupffer cells can generate ROS by NAD PH oxidase that pro motes hepatocyte proliferation and inhibition of apoptosis.PPARγagonist carcinogenicity is generally caused by bladder stone.The carcinogenicity of PPAR agonists to humans has not been confirmed,but the carcinogenic potential of these drugs can-not be ignored.

OBJECTIVE To study the toxicity of zinc oxide nanoparticles (ZnO-NPs) on murine macrophage Ana-1 cells and the mechanism.METHODS Ana-1 cells were incubated with ZnO-NP (2.5-160 mg· L-1).Cell viability was investigated by MTT assay.The integrity of cell membrane was investigated by acridine orange-ethidium bromide (AO-EB) staining.The intracellular uptake of ZnO-NP and the percentage of sub-G1 of Ana-1 cells were detected by flow cytometry.Zinc ions were determined by fluorescent probe.The change of cell viability was studied after chelating zinc ions with ethylene diamine tetraacetic acid (EDTA).RESULTS ZnO-NP 2.5,5,10 and 20 mg· L-1 decreased cell viability of Ana-1 cells (r=0.905,P＜0.05) in a concentration-dependent manner.The cell viability was decreased to 27.9％ after exposure to ZnO-NP 20 mg· L-1.Intracellular uptake of ZnO-NP was increased after Ana-1 cell incubated with ZnO-NP at concentrations ranging from 40 to 160 mg· L-1 (P＜0.05).There were obvious free zinc ions in the cells.EDTA 2.5 mmol· L-1 significantly increased the cell viability decreased by ZnO-NP 20 mg· L-1 (P＜0.05).Chelating free zinc ions significantly mitigated ZnO-NP induced cell toxicity (P＜0.05).CONCLUSION Cytotoxicity and apoptosis of Ana-1 cells induced by ZnO-NP might be related to intracellular uptake of ZnO-NP and release of zinc ions.

A technique based on release of the human atrial natriuretic peptide (hANP) from plasmid hANP cDNA transfected Chinese hamster ovary (CHO) cells encapsulated in polycaprolactone (PCL)-capsules was used for a potential therapeutic approach to hypertension or congestive heart failure (CHF). The plasmid combining with hANP cDNA was transfected into CHO cells, and then encapsulated plasmid hANP cDNA transfected CHO cells were implanted into two-kidney, one-clip (2K1C) hypertensive rats intraperitoneally. The morphological changes, histological changes were investigated after the implantation of PCL-capsules in 2K1C hypertensive rats. The results showed that the implantation of encapsulated hANP-producing cells caused a significant delay of blood pressure (BP) increase after the encapsulated cells being implanted in 2K1C hypertensive rats. These effects were reflected morphologically by an attenuation of the glomerular sclerotic lesions, tubular damage and renal arterial thickening, comparing with control group. The plasma levels of hANP in 2K1C rats implanted with the PCL-capsules containing hANP-producing cells were higher than that of the control rats. These results demonstrated the usefulness of encapsulated hANP gene transfected cells as a new tool for hANP gene delivery in studying renovascular hypertension and cardiovascular diseases, thus implying the potential of using gene transfected cells as therapeutic agents in the treatment of cardiovascular diseases.
Animals ; Atrial Natriuretic Factor ; biosynthesis ; genetics ; therapeutic use ; CHO Cells ; Capsules ; Cell Transplantation ; Cricetinae ; DNA, Complementary ; biosynthesis ; genetics ; Genetic Therapy ; methods ; Humans ; Hypertension, Renovascular ; pathology ; therapy ; Kidney ; pathology ; Male ; Plasmids ; Rats ; Rats, Wistar ; Recombination, Genetic ; Transfection ; Transgenes

Objective To analyze the constituent of the 32 kD protein band and its expression in schizophrenia se?rum. Methods Sixty schizophrenia patients and 58 health controls were recruited. The serum samples were collected and precipitated with 7%PEG. The sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) was used to ob?tain the abnormal 32 kD proteins band in patients. This protein band was cut and then analyzed using mass spectrometric technique. Results The 32 kD protein band was present in 38 schizophrenia patients but not in control and positive rate was 63.33%. The mass spectrometric analysis showed that 32 kD protein band contained 14 proteins ranging from 30 kD to 35 kD, including 6 high-frequency proteins (cDNA coded protein 1 and 2, Apolin protein A-1, Isoform 2 of ficolin-2, Complement factor H and clusterin) and 8 low-frequency proteins (IgG H chain, zinc-alphg-2-glycoprotein, fermitin,family apolin protein L-1, isoform 10 of collectin-1, purine nucleoside, anne xin and cDNA coded protein 3). Three cD?NA coded unknown proteins were highly similar to complement C4-B, β2-glycoprotein and erythrocyte band 7 integral membrane protein. Conclusion There is a unknown specific 32 kD protein that is consisted mainly of fourteen proteins in serum of schizophrenia.