Leukemia Inhibitory Factor Decreases Neurogenesis and Angiogenesis in a Rat Model of Intracerebral Hemorrhage.

Neurogenesis and angiogenesis can improve the neurologic function after intracerebral hemorrhage (ICH). Leukemia inhibitory factor (LIF) plays an important role in neurogenesis and angiogenesis. In this study, a rat model of autologous blood-induced ICH was used to evaluate the effect of LIF on the neurogenesis and angiogenesis following ICH. After ICH, LIF-positive neurons and dilated vessels were detected in the peri-hematomal region. It was found that LIF levels increased significantly and peaked 14 days after ICH induction. Double immunofluorescence confirmed that LIF was expressed in neurons and endothelial cells. ICH also led to increases of doublecortin (DCX)- and von Willebrand factor (vWF)-positive cells as well as proliferation of cell nuclear antigen (PCNA)+/DCX+ and PCNA+/vWF+ nuclei. All these ICH-induced increases were significantly attenuated by exogenous LIF infusion. These data suggested that LIF was a negative regulator of neurogenesis and angiogenesis after ICH.

Employing the Sirolimus-Eluting Poly (Propylene Carbonate) Mesh for the Prevention of Arteriovenous Graft Stenosis in Rats.

Poly (propylene carbonate, PPC) is a new member of the aliphatic polyester family. An outstanding feature of PPC is that it produces mainly water and carbon dioxide when degraded in vivo, causing minimal side effects. This unique property together with excellent biocompatibility and biodegradability makes PPC a promising material for drug delivery. In this study, we explored the effect of the sirolimus (an inhibitor of cell growth)-eluting PPC mesh on graft stenosis and its possible mechanisms in a rat arteriovenous grafting model. The PPC mesh was prepared by electrospinning. A jugular vein to abdominal aortic autograft transplantation model was established in rats. The graft was then treated by wrapping with the drug mesh or the drug-free mesh or left untreated. Four weeks posttransplantation, neointima was measured with hematoxylin and eosin staining, matrix metalloproteinase-2 (MMP-2), and MMP-9, and proliferating cell nuclear antigen (PCNA) in the grafts were assayed by Western blotting and immunohistochemistry, respectively. In vitro rat aortic adventitial fibroblast cell (RAAFC) migration was assessed using the Boyden chamber assay, and phospho-mammalian target of rapamycin (mTOR) levels in RAAFCs were determined by Western blotting. Animals with the drug mesh had an intimal area index of 4.87% ± 0.98%, significantly lower than that of the blank group (14.21% ± 2.56%) or the PPC group (15.03% ± 2.35%, both P < .05). The sirolimus mesh markedly suppressed MMP-2 and MMP-9 expression, decreased PCNA-positive cell numbers, inhibited RAAFC migration, and reduced phospho-mTOR levels. Our data suggest that the sirolimus-eluting PPC mesh might be potentially applied for the management of grafting stenosis.

Detection of low-abundance point mutations by competitive strand assisted endonuclease IV signal amplification system.

Genetic mutations are important molecular biomarkers for cancer diagnosis and surveillance. Therefore, the development of methods for mutation detection characterized with straightforward, highly specific and sensitive to low-level mutations within various sequence contexts is extremely needed. Although some of the currently available methods have shown very encouraging results, their discrimination efficiency is still very low. Herein, we demonstrate a fluorescent probe coupled with blocker and property of melting temperature discrimination, which is able to identify the presence of known or unknown single-base variations at abundances down to 0.1% within 20 min. The discrimination factors between the perfect-match target and single-base mismatched target are determined to be 10.15-38.48. The method is sequence independent, which assures a wide range of application. The new method would be an ideal choice for high-throughput in vitro diagnosis and precise clinical treatment.

Detection of Low-abundance Point Mutations by Competitive Strand Assisted Endonuclease Ⅳ Signal Amplification System / 华中科技大学学报（医学）（英德文版）

Genetic mutations are important molecular biomarkers for cancer diagnosis and surveillance.Therefore,the development of methods for mutation detection characterized with straightforward,highly specific and sensitive to low-level mutations within various sequence contexts is extremely needed.Although some of the currently available methods have shown very encouraging results,their discrimination efficiency is still very low.Herein,we demonstrate a fluorescent probe coupled with blocker and property of melting temperature discrimination,which is able to identify the presence of known or unknown single-base variations at abundances down to 0.1％ within 20 min.The discrimination factors between the perfect-match target and single-base mismatched target are determined to be 10.15-38.48.The method is sequence independent,which assures a wide range of application.The new method would be an ideal choice for high-throughput in vitro diagnosis and precise clinical treatment.

Pre-treatment with bone marrow-derived mesenchymal stem cells inhibits systemic intravascular coagulation and attenuates organ dysfunction in lipopolysaccharide-induced disseminated intravascular coagulation rat model.

BACKGROUND: Bacterial lipopolysaccharide (LPS) can activate immunological cells to secrete various proinflammatory cytokines involved in the pathophysiological process of disseminated intravascular coagulation (DIC) during infection. In recent years, it has been found that bone marrow-derived mesenchymal stem cells (BMSCs) can affect the activity of these immune cells and regulate the secretion of proinflammatory cytokines. Here, we report the possible protective effect of BMSCs pre-treatment in LPS-induced DIC rat model and the mechanism. METHODS: Forty-eight adult male rats were divided into five experimental groups and one control group with eight animals in each group. In the treatment groups, 0, 1'10(6), 2'10(6), 3'10(6), and 5'10(6) of BMSCs were injected intravenously for 3 days before LPS injection, while the control group was treated with pure cell culture medium injection. Then, the LPS (3 mg/kg) was injected via the tail vein in the treatment groups, while the control group received 0.9% NaCl. Blood was withdrawn before and 4 and 8 hours after LPS administration. The following parameters were monitored: platelets (PLT), fibrinogen (Fib), D-dimer (D-D), activated partial thromboplastin time (APTT), prothrombin time (PT), tumor necrosis factor-a (TNF-a), interferon-g (IFN-g), interleukin-1b (IL-1b), creatinine (Cr), alanine aminotransferase (ALT), creatinine kinase-MB (CK-MB), and endothelin (ET). RESULTS: Compared with the control group, a significant change of coagulation parameters were found in the experimental groups. The plasma level of the inflammatory mediator (TNF-a, IFN-g, IL-1b), organ indicator (Cr, ALT, and CK-MB), and ET in the experimental groups were much lower (P < 0.05) than that in the control group. Furthermore, some of these effects were dose-dependent; the statistical comparison of the plasma levels between the groups (from group 2 to group 5) showed a significant difference (P < 0.05), except the ALT and CK-MB levels (P > 0.05). CONCLUSION: Pre-treatment with BMSCs can attenuate organ dysfunction and inhibit systemic intravascular coagulation effectively via the regulatory effect on immune cells and proinflammatory cytokines in LPS-induced DIC rat model.