Studies involving the use of prenatally programmed hypertension have been shown to potentially contribute to prevention of essential hypertension (EH). Our previous research has demonstrated that prenatal inflammatory stimulation leads to offspring’s aortic dysfunction and hypertension in pregnant Sprague-Dawley rats challenged with lipopolysaccharide (LPS). The present study found that prenatal LPS exposure led to NF-κB dyshomeostasis from fetus to adult, which was characterized by PI3K-Akt activation mediated degradation of IκBα protein and impaired NF-κB self-negative feedback loop mediated less newly synthesis of IκBα mRNA in thoracic aortas ( gestational day 20, postnatal week 7 and 16 ). Prenatal or postnatal exposure of the IκBα degradation inhibitor, pyrollidine dithiocarbamate, effectively blocked NF-κB activation, endothelium dysfunction and renin-angiotensin system (RAS) over-activity in thoracic aortas, resulting in reduced blood pressure in offspring that received prenatal exposure to LPS. Surprisingly, NF-κB dyshomeostasis and RAS over-activity were only found in thoracic aortas but not in superior mesenteric arteries. Collectively, our data demonstrate that the early life NF-κB dyshomeostasis induced by prenatal inflammatory exposure plays an essential role in the development of EH through triggering RAS over-activity. We conclude that early life NF-κB dyshomeostasis is a key predictor of EH and thus, NF-κB inhibition represents an effective interventional strategy for EH prevention.
The CCQM-K97 key comparison was organized by the inorganic analysis working group (IAWG) of CCQM as a follow-up to completed pilot study CCQM-P96 and P96.1 to test the abilities of the national metrology institutes to accurately quantitate the mass fraction of arsenobetaine (AsB) in standard solution and in fish tissue. A pilot study CCQM-P133 was parallelized with this key comparison. National Institute of Metrology (NIM), China and National Metrology Institute of Japan (NMIJ) acted as the coordinating laboratories. Six NMIs participated in CCQM-K97 and two institutes participated in CCQM-P133, and all of them submitted the results. Some NMIs submitted more than one results by different methods. The results were in excellent agreement with each other, and obviously better than those of previous P96 and P96.1. Therefore the calibrant which each NMI used was comparable. It shows that the capabilities of some of the participants have been improved after the previous pilot studies. Main text To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by the CCQM, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).
The self-assembling peptide, RAD16-II (Ac-RARADADARARADADA-NH2), has been shown to have many great applications in nanotechnology and tissue engineering. But few studies have been carried out to study the application of self-assembling peptides as a drug carrier. We used hydrophobic drug pyrene as a model and liposome vesicles to mimic bilayer membranes to study the ability of RAD16-II in drug encapsulation and transfer to lipid vesicles. It was found that this designed self-assembling peptide was able to stabilize hydrophobic drug in aqueous solution and deliver it into lipophilic environment. Analysis of the fluorescence excitation spectra showed that pyrene was present in the crystalline form when stabilized by RAD16-II and was able to be dispersed in egg phosphatidylcholine vesicles. This suggested that pyrene was completely released from RAD-Py mixture into the bilayer membranes. Furthermore, the concentration of pyrene transferred into the vesicles was quantified and its transfer rate was determined. The scanning electron micrograph image showed that pyrene microcrystals and peptide were absorbed by each other and the size of the pyrene-peptide complexes was larger than 10 microm. These data further demonstrated that this type of ionic complementary oligopeptides was able to significantly encapsulate hydrophobic drug and provide a new type of nanomaterials for delivering drugs.
ENATBIO: a National Conference on Emerging Nanoscience in Technology and Biomedicine Guangzhao Mao, PhD, Golam Newaz, Chiming Wei, MD, PhD⁎ Department of Chemical Engineering and Materials Science, Wayne State University, Detroit, Michigan, USA Department of Mechanical Engineering, Wayne State University, Detroit, Michigan, USA Department of Surgery, Johns Hopkins University School of Medicine, Ellicott City, Maryland, USA
Nanomedicine is the medical diagnosis, monitoring and applying treatment at the level of single molecules or molecular assemblies that provide structure, control, signals, homeostasis, and motility in living cells. Quantum dots (QDs) are nanometer-sized fluorescent probes suitable for advanced biological imaging. The nanotechnology will be very useful for the drug delivery and diagnostic approach. The development of a cancer therapy monitoring/diagnostic platform device such a device is intended to provide near real time monitoring of patient blood for cancer cells, cell derived nanoparticulates, such as high molecular weight DNA fragments.
This article describes the use of nanobiologic techniques in diagnosis and preventive medicine. It discusses the engineering of fluorescent and bioluminescent proteins to visualize biologic functions; single-molecule measurements of protein structure and function; two-photon microscopy for molecular imaging of the structure and function in living cells and tissues; and imaging ligand-induced protein conformations and interactions by fluorescence in single living cells.
The Third Annual Meeting of the American Academy of Nanomedicine (AANM) was held at the University of California San Diego, in San Diego, California during September 7-8, 2007. The meeting was focused on successful translational nanomedicine: from bench to bedside. There were four keynote lectures and eight scientific symposiums in this meeting. The researchers and investigators reported the results and process of current nanomedicine research and approaches to clinical applications. The meeting provided exciting information for nanomedicine clinical-related researches and strategy for further development of nanomedicine research which will be benefits to clinical practice.
This article discusses the use of nanotechnology in drug delivery approaches. Magnetic nanotechnology is finding wide applications in medicine, most notably in MRI and magnetic separation. The impedance biosensor is expected to find applications in monitoring cytokines in cancer, bone turnover markers in osteoporosis, and understanding neural-degenerative diseases.
AIMS We investigated whether hypoxia-inducible factor 1 alpha (HIF-1 alpha) plays a role in the acute phase of ischaemic preconditioning (IPC). METHODS AND RESULTS Hearts from wild-type (WT) mice and mice heterozygous for a null allele at the locus encoding HIF-1 alpha (HET) were subjected to IPC (10-min ischaemia/5 min reperfusion, or two cycles of 5 min ischaemia/5 min reperfusion), followed by 30 min ischaemia and reperfusion. Left ventricular-developed pressure, heart rate, and coronary flow rate were measured continuously. Apoptosis and infarct size were assessed by TUNEL assay, cleaved caspase 3 immunohistochemistry, and triphenyltetrazolium chloride staining. Production of reactive oxygen species (ROS) in isolated cardiac mitochondria was measured by a chemiluminescence assay. The phosphatase and tensin homologue (PTEN) and AKT (protein kinase B) were analysed by immunoblot assay. IPC improved functional recovery and limited infarct size and apoptosis after prolonged ischaemia-reperfusion in WT hearts, but not in HET hearts. Mitochondrial ROS production, PTEN oxidation, and AKT phosphorylation were impaired in HET hearts. WT and HET hearts were protected by adenosine, which acts via an ROS-independent mechanism. CONCLUSION HIF-1 alpha is required for IPC-induced mitochondrial ROS production and myocardial protection against ischaemia-reperfusion injury.