Regulating effects of Semen Nigellae extract on vascular endothelial cells and angiogenesis / 中国药理学通报

Aim To investigate the effects of Semen Nigellae extract on regulating endothelial functions and angiogenesis and the underlying mechanisms.Methods After the extract of Semen Nigellae was obtained,the extract was administered to the primarily cultured rat aortic endothelial cells (RAECs).Then,the tube formation,proliferation and migration ability of RAECs were examined,and the expression of angiogenesis-related signaling pathways proteins,such as transforming growth factor-betal (TGF-β1),Smad3,platelet derived growth factor receptor(PDGFR),Cx43,Akt and endothelial nitric oxide synthase (eNOS),were detected via Western blot analysis.Meanwhile,production of nitric oxide(NO) from RAECs was also measured after treatment with the extract of Semen Nigellae.Results The extract of Semen Nigellae significantly promoted the tube formation,proliferation and migration of RAECs in a dose-dependent manner.The protein expressions of TGF-β1,Smad3,PDGFR,Cx43,Akt and eNOS,as well as phosphorylation levels of Akt and eNOS,in RAECs were also markedly elevated by the administration of Semen Nigellae.In addition,the production of NO was notably enhanced by the extract of Semen Nigellae.Conclusions The extract of Semen Nigellae may improve endothelial functions and angiogenesis by activating Akt-eNOS and TGF-β1-Smad3 pathway.Meanwhile,it may also promote the maturation and stability of nascent vasculatures by activating the PDGFR and Cx43-related signaling pathways.Hence,Semen Nigellae may be a new therapeutic drug for ischemic diseases.

Results of Carotid Doppler and Lipid Profiles in Patients with Ocular Ischemic Disease

PURPOSE: To analyze the findings of carotid Doppler and lipid profiles in patients with ischemic ocular disease and as well as the risk and correlation between cardiovascular and ischemic ocular diseases. METHODS: We analyzed the intima-media thickness (IMT) and existence of vascular stenosis using carotid Doppler and blood lipid profiles of the study patients diagnosed with anterior ischemic optic neuropathy (AION group, n = 45), central retinal vein occlusion (CRVO group, n = 34), central retinal artery occlusion (CRAO group, n = 23), or ocular ischemic syndrome (OIS group, n = 27). The study patients who visited Chonbuk National University Hospital from January, 2010 to June, 2013 were compared with healthy control (control group, n = 107). RESULTS: The average age of the study patients was 60.0 +/- 14.1 years and 56.1 +/- 9.1 years for the controls. Ipsilateral common carotid artery-IMT was thicker in the OIS and CRAO groups than the control group (p < 0.01 and <0.01, respectively). The number of patients with carotid stenosis was highest in the OIS group (n = 17, 62.9%) followed by the CRAO group (n = 5, 21.7%), CRVO group (n = 2, 5.9%), and AION group (n = 1, 2.2%). No significant stenosis was found in the control group. Total blood cholesterol was not significantly different between the study patients and controls. Low-density lipoprotein cholesterol was higher in every patient group than the control group (p < 0.01, <0.01, <0.05 and <0.01, respectively). CONCLUSIONS: The ischemic ocular disease likely precedes carotid artery disease and dyslipidemia. Therefore, general examinations such as carotid Doppler, lipid profile and risk factor evaluations are needed in patients with ischemic ocular disease.

It is Time That Health Authorities Promote the Use of Oxygen-ozone Therapy as an Integrative Therapy of Orthodox Drugs.

Ozone is a very reactive gas and is toxic for the respiratory system but, under precise rules, it can be therapeutically useful for human disease with a chronic oxidative stress. An unfavorable combination of factors such as a wrong dogma, the fact that ozone is one of the worst troposphere pollutants and past misuse of ozone have led to a poor consideration of ozone therapy. However, basic and clinical work, developed during the last two decades, clarified both the biochemical and molecular mechanisms of action of ozone in biology and medicine. A judicious dose of ozone dissolved in blood immediately triggers a cascade of well defined chemical compounds acting on multiple cellular targets according to well-known biochemical and molecular pathways. Ozone therapy is proving to be very useful in the dry form of age-related macular degeneration (AMD), cardiovascular diseases, chronic obstructive pulmonary disease (COPD), cerebral diseases and healing disorders, where conventional medicine appears insufficient and too expensive. It is time that World Health Authorities abandon prejudice and skepticism and start to take advantage of an integrative medical application able to help the majority of world population.

Gene expression promoted by the SV40 DNA targeting sequence and the hypoxia-responsive element under normoxia and hypoxia

The main objective of the present study was to find suitable DNA-targeting sequences (DTS) for the construction of plasmid vectors to be used to treat ischemic diseases. The well-known Simian virus 40 nuclear DTS (SV40-DTS) and hypoxia-responsive element (HRE) sequences were used to construct plasmid vectors to express the human vascular endothelial growth factor gene (hVEGF). The rate of plasmid nuclear transport and consequent gene expression under normoxia (20 percent O2) and hypoxia (less than 5 percent O2) were determined. Plasmids containing the SV40-DTS or HRE sequences were constructed and used to transfect the A293T cell line (a human embryonic kidney cell line) in vitro and mouse skeletal muscle cells in vivo. Plasmid transport to the nucleus was monitored by real-time PCR, and the expression level of the hVEGF gene was measured by ELISA. The in vitro nuclear transport efficiency of the SV40-DTS plasmid was about 50 percent lower under hypoxia, while the HRE plasmid was about 50 percent higher under hypoxia. Quantitation of reporter gene expression in vitro and in vivo, under hypoxia and normoxia, confirmed that the SV40-DTS plasmid functioned better under normoxia, while the HRE plasmid was superior under hypoxia. These results indicate that the efficiency of gene expression by plasmids containing DNA binding sequences is affected by the concentration of oxygen in the medium.