Cause of Cambrian Explosion - Terrestrial or Cosmic?

We review the salient evidence consistent with or predicted by the Hoyle-Wickramasinghe (H-W) thesis of Cometary (Cosmic) Biology. Much of this physical and biological evidence is multifactorial. One particular focus are the recent studies which date the emergence of the complex retroviruses of vertebrate lines at or just before the Cambrian Explosion of ∼500 Ma.

Intrablastocyst injection with human CD34+/CD133+ cells increase survival of immunocompetent fumarylacetoacetate hydrolase knockout mice.

Mice harbouring a humanized liver represent a powerful tool for translating preclinical studies of drug metabolism and pharmacokinetics into humans, as well as the exploitation of basic studies on liver pathophysiology including hepatitis C virus (HCV) infection. Human adult stem cells injected into immunocompetent mice at preimmune stages of development, generate chimeric animals harbouring a liver with relatively discrete foci of human hepatocyte-like cells. In this study, we have evaluated whether similar protocol of xenotransplantation in the presence of selective pressure might lead to a higher human-into-mouse liver repopulation, leading to a relevant improvement of liver function.

Unique antineoplastic profile of Saquinavir-NO, a novel NO-derivative of the protease inhibitor Saquinavir, on the in vitro and in vivo tumor formation of A375 human melanoma cells.

We have recently shown that covalent attachment of the nitric oxide (NO) moiety to the HIV protease inhibitor Saquinavir (Saq) produced a qualitatively new chemical entity, named Saquinavir-NO (Saq-NO), with enhanced anticancer properties and reduced toxicity both in vitro and in vivo. The aim of this study was to address several unanswered questions both on the pharmacological profile of Saq-NO as well as on the in vivo role of NO in the oncogenesis of A375 human melanoma cells. To this end, we have evaluated here the impact of single and combined effects of Saq-NO, Saq, the NO-donor DETA NONOate and the iNOS inhibitor L-NAME on the in vitro as well as in vivo growth of the iNOS positive A375 cells.

Potent inhibitors of subgenomic hepatitis C virus RNA replication through optimization of indole-N-acetamide allosteric inhibitors of the viral NS5B polymerase.

Infections caused by hepatitis C virus (HCV) are a significant world health problem for which novel therapies are in urgent demand. Compounds that block replication of subgenomic HCV RNA in liver cells are of interest because of their demonstrated antiviral effect in the clinic. In followup to our recent report that indole-N-acetamides (e.

Human hepatocytes in mice receiving pre-immune injection with human cord blood cells.

It is well established that certain subpopulations of human adult stem cells can generate hepatocyte-like cells when transplanted into adult immunosuppressed mice. In the present study, we wanted to explore whether xeno-transplantation of human cord blood CD34(+) (hCBCD34(+)) cells during pre-immune stages of development in immunocompetent mice might also lead to human-mouse liver chimerism. Freshly isolated hCBCD34(+) cells were xeno-transplanted into non-immunosuppressed mice by both intra-blastocyst and intra-fetal injections.

p21(Waf1/Cip1/Sdi1) mediates shear stress-dependent antiapoptotic function.

Objective: The antiapoptotic effect of p21(Waf1/Cip1/Sdi1) (p21) was examined in human umbilical vein endothelial cells (HUVEC) exposed to laminar shear stress (SS) or to the nitric oxide donor sodium nitroprusside (SNP) and in a mouse model of hindlimb ischemia.

Methods: In vitro: Cells were cultured without serum and in the presence of cobalt chloride to simulate hypoxia for 12 h (T0). Shear stress was applied to endothelial cells for additional 12 h.