Persistence of hepatic hepatitis B virus after serological clearance of HBsAG with autologous peripheral stem cell transplantation

Delayed clearance of hepatitis B surface antigen was previously reported in a 38 year old woman after high dose chemotherapy with autologous peripheral blood stem cell rescue. Sixteen months later, this patient remained hepatitis B surface antigen negative, hepatitis B surface anti-body positive, and serum hepatitis B DNA negative by polymerase chain reaction. Serial liver biopsies (one at hepatitis B e antigen positive stage, one at hepatitis B e antibody positive stage, and one at hepatitis B surface antigen negative and hepatitis B surface antibody positive stage) showed a gradual resolution of the inflammatory activity with loss of hepatitis B e antigen and then hepatitis B surface antigen in the serum. However, the degree of fibrosis, though mild, remained the same. With the serological clearance of hepatitis B surface antigen, a small amount of hepatitis B virus DNA was still detectable in the nuclei of liver cells.published_or_final_versio

Suppression of tumorigenesis and metastasis of hepatocellular carcinoma by shRNA interference targeting on homeoprotein Six1

We previously demonstrated that the overexpression of homeoprotein Six1 in hepatocellular carcinoma (HCC) patients is associated with venous infiltration, advanced pathologic tumor metastasis (pTNM) stage and poor overall survival rate (Ng et al. Br J Cancer 2006;95:1050-5). In this study, short hairpin RNA (shRNA) interference approach was used to suppress the expression of Six1 in a metastatic HCC cell line MHCC97L. Stable transfectant MHCC97L-shSix1 carrying Six1-specific shRNA plasmid was established to downregulate Six1 expression to about 40% when compared with MHCC97L-Control. In vitro functional assays demonstrated that the growth rate and proliferation ability of MHCC97L-shSix1 cells were markedly decreased. Moreover, significant decrease of cell motility and invasiveness were observed in MHCC97L-shSix1 cells. Data from in vivo xenograft tumorigenesis model demonstrated that the size of tumor in MHCC97L-shSix1 group was dramatically reduced. Experimental and spontaneous metastasis models indicated that targeting Six1 suppression noticeably reduced the pulmonary metastasis in MHCC97L-shSix1 group. To identify Six1-regulated targets, cDNA microarray was employed to compare the expression profiles of MHCC97L-Control and MHCC97L-shSix1 cells. Twenty-eight downregulated and 24 upregulated genes with known functions were identified in MHCC97L-shSix1. The functions of these target genes are involved in diverse biological activities. Our data suggest that Six1 may be involved in regulation of proliferation and invasiveness of HCC; thus targeting suppression of Six1 is a viable option for treating HCC patients. © 2009 UICC.postprin

Modification of upper-ocean temperature structure by subsurface mixing in the presence of strong salinity stratification

Author Posting. © The Oceanography Society, 2016. This article is posted here by permission of The Oceanography Society for personal use, not for redistribution. The definitive version was published in Oceanography 29, no. 2 (2016): 62–71, doi:10.5670/oceanog.2016.39.The Bay of Bengal has a complex upper-ocean temperature and salinity structure that is, in places, characterized by strong salinity stratification and multiple inversions in temperature. Here, two short time series from continuously profiling floats, equipped with microstructure sensors to measure subsurface mixing, are used to highlight implications of complex hydrography on upper-ocean heat content and the evolution of sea surface temperature. Weak mixing coupled with the existence of subsurface warm layers suggest the potential for storage of heat below the surface mixed layer over relatively long time scales. On the diurnal time scale, these data demonstrate the competing effects of surface heat flux and subsurface mixing in the presence of thin salinity-stratified mixed layers with temperature inversions. Pre-existing stratification can amplify the sea surface temperature response through control on the vertical extent of heating and cooling by surface fluxes. In contrast, subsurface mixing entrains relatively cool water during the day and relatively warm water during the night, damping the response to daytime heating and nighttime cooling at the surface. These observations hint at the challenges involved in improving monsoon prediction at longer, intraseasonal time scales as models may need to resolve upper-ocean variability over short time and fine vertical scales.This work was funded by Office of Naval Research grants N00014-14-1-0236 (ELS, JNM), N00014-13-1-0483 (DLR), N00014-13-1- 0453 (JTF), and N00014-12-1-0938 (SKV, AG)

Efimov physics beyond three particles

Efimov physics originally refers to a system of three particles. Here we review recent theoretical progress seeking for manifestations of Efimov physics in systems composed of more than three particles. Clusters of more than three bosons are tied to each Efimov trimer, but no independent Efimov physics exists there beyond three bosons. The case of a few heavy fermions interacting with a lighter atom is also considered, where the mass ratio of the constituent particles plays a significant role. Following Efimov's study of the (2+1) system, the (3+1) system was shown to have its own critical mass ratio to become Efimovian. We show that the (4+1) system becomes Efimovian at a mass ratio which is smaller than its sub-systems thresholds, giving a pure five-body Efimov effect. The (5+1) and (6+1) systems are also discussed, and we show the absence of 6- and 7-body Efimov physics there

Suppression of liver tumor growth and metastasis by adiponectin in nude mice through inhibition of tumor angiogenesis and downregulation of rho kinase/IFN-inducible protein 10/matrix metalloproteinase 9 signaling

Purpose: We aimed to investigate the effects of adiponectin on liver cancer growth and metastasis and explore the underlying mechanisms. Experimental Design: An orthotopic liver tumor nude mice model with distant metastatic potential was applied. Either Ad-adiponectin (1 × 10 8; treatment group) or Ad-luciferase (control group) was injected via portal vein after tumor implantation. Tumor growth and metastasis were monitored by Xenogen In vivo Imaging System. Hepatic stellate cell activation by α-smooth muscle actin staining, microvessel density by CD34 staining, macrophage infiltration in tumor tissue, and cell signaling leading to invasion, migration [Rho kinase (ROCK), IFN-inducible protein 10 (IP10), and matrix metalloproteinase 9], and angiogenesis [vascular endothelial growth factor (VEGF) and angiopoietin 1] were also compared. Tumor-nontumor margin was examined under electron microscopy. Direct effects of adiponectin on liver cancer cells and endothelial cells were further investigated by a series of functional studies. Results: Tumor growth was significantly inhibited by adiponectin treatment, accompanied by a lower incidence of lung metastasis. Hepatic stellate cell activation and macrophage infiltration in the liver tumors were suppressed by adiponectin treatment, along with decreased microvessel density. The treatment group had less Ki-67-positive tumor cells and downregulated protein expression of ROCK1, proline-rich tyrosine kinase 2, and VEGF. Tumor vascular endothelial cell damage was found in the treatment group under electron microscopy. In vitro functional study showed that adiponectin not only downregulated the ROCK/IP10/VEGF signaling pathway but also inhibited the formation of lamellipodia, which contribute to cell migration. Conclusion: Adiponectin treatment significantly inhibited liver tumor growth and metastasis by suppression of tumor angiogenesis and downregulation of the ROCK/IP10/matrix metalloproteinase 9 pathway. ©2010 AACR.postprin

Self-rated health in middle-aged and elderly Chinese : distribution, determinants and associations with cardio-metabolic risk factors

Background: Self-rated health (SRH) has been demonstrated to be an accurate reflection of a person's health and a valid predictor of incident mortality and chronic morbidity. We aimed to evaluate the distribution and factors associated with SRH and its association with biomarkers of cardio-metabolic diseases among middle-aged and elderly Chinese. Methods: Survey of 1,458 men and 1,831 women aged 50 to 70 years, conducted in one urban and two rural areas of Beijing and Shanghai in 2005. SRH status was measured and categorized as good (very good and good) vs. not good (fair, poor and very poor). Determinants of SRH and associations with biomarkers of cardio-metabolic diseases were evaluated using logistic regression. Results: Thirty two percent of participants reported good SRH. Males and rural residents tended to report good SRH. After adjusting for potential confounders, residence, physical activity, employment status, sleep quality and presence of diabetes, cardiovascular disease, and depression were the main determinants of SRH. Those free from cardiovascular disease (OR 3.68; 95%CI 2.39; 5.66), rural residents (OR 1.89; 95% CI 1.47; 2.43), non-depressed participants (OR 2.50; 95% CI 1.67; 3.73) and those with good sleep quality (OR 2.95; 95% CI 2.22; 3.91) had almost twice or over the chance of reporting good SRH compared to their counterparts. There were significant associations -and trend- between SRH and levels of inflammatory markers, insulin levels and insulin resistance. Conclusion: Only one third of middle-aged and elderly Chinese assessed their health status as good or very good. Although further longitudinal studies are required to confirm our findings, interventions targeting social inequalities, lifestyle patterns might not only contribute to prevent chronic morbidity but as well to improve populations' perceived health

Dengue Virus-Infected Dendritic Cells, but Not Monocytes, Activate Natural Killer Cells through a Contact-Dependent Mechanism Involving Adhesion Molecules

Natural killer (NK) cells play a protective role against dengue virus (DENV) infection, but the cellular and molecular mechanisms are not fully understood. Using an optimized humanized mouse model, we show that human NK cells, through the secretion of gamma interferon (IFN-γ), are critical in the early defense against DENV infection. Depletion of NK cells or neutralization of IFN-γ leads to increased viremia and more severe thrombocytopenia and liver damage in humanized mice. In vitro studies using autologous human NK cells show that DENV-infected monocyte-derived dendritic cells (MDDCs), but not monocytes, activate NK cells in a contact-dependent manner, resulting in upregulation of CD69 and CD25 and secretion of IFN-γ. Blocking adhesion molecules (LFA-1, DNAM-1, CD2, and 2β4) on NK cells abolishes NK cell activation, IFN-γ secretion, and the control of DENV replication. NK cells activated by infected MDDCs also inhibit DENV infection in monocytes. These findings show the essential role of human NK cells in protection against acute DENV infection in vivo, identify adhesion molecules and dendritic cells required for NK cell activation, and delineate the sequence of events for NK cell activation and protection against DENV infection.IMPORTANCE Dengue is a mosquito-transmitted viral disease with a range of symptoms, from mild fever to life-threatening dengue hemorrhagic fever. The diverse disease manifestation is thought to result from a complex interplay between viral and host factors. Using mice engrafted with a human immune system, we show that human NK cells inhibit virus infection through secretion of the cytokine gamma interferon and reduce disease pathogenesis, including depletion of platelets and liver damage. During a natural infection, DENV initially infects dendritic cells in the skin. We find that NK cells interact with infected dendritic cells through physical contact mediated by adhesion molecules and become activated before they can control virus infection. These results show a critical role of human NK cells in controlling DENV infection in vivo and reveal the sequence of molecular and cellular events that activate NK cells to control dengue virus infection

Generation of three-dimensional multiple spheroid model of olfactory ensheathing cells using floating liquid marbles

We describe a novel protocol for three-dimensional culturing of olfactory ensheathing cells (OECs), which can be used to understand how OECs interact with other cells in three dimensions. Transplantation of OECs is being trialled for repair of the paralysed spinal cord, with promising but variable results and thus the therapy needs improving. To date, studies of OEC behaviour in a multicellular environment have been hampered by the lack of suitable three-dimensional cell culture models. Here, we exploit the floating liquid marble, a liquid droplet coated with hydrophobic powder and placed on a liquid bath. The presence of the liquid bath increases the humidity and minimises the effect of evaporation. Floating liquid marbles allow the OECs to freely associate and interact to produce OEC spheroids with uniform shapes and sizes. In contrast, a sessile liquid marble on a solid surface suffers from evaporation and the cells aggregate with irregular shapes. We used floating liquid marbles to co-culture OECs with Schwann cells and astrocytes which formed natural structures without the confines of gels or bounding layers. This protocol can be used to determine how OECs and other cell types associate and interact while forming complex cell structuresJSJ was funded by a grant from the Perry Cross Spinal Research Foundation; NTN was funded from Griffith University through a start-up grant and a grant from the Griffith University Research Infrastructure Program; JAK was funded by an Australian Research Council Discovery Grant DP150104495; JT was funded by an Eskitis Institute scholarship; CO was funded by a Griffith Sciences scholarship; RV was funded by a Griffith University International Postgraduate Research Scholarshi

Clinical relevance and therapeutic potential of angiopoietin-like protein 4 in hepatocellular carcinoma

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